«Антипролиферативное действие карнозина и его производных на опухолевые клетки нейрального происхождения ...»
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ADDIN EN.CITE.DATA [211, 212]. BHMF и RNO представляют собой ловушки синглетного кислорода (1О2), ингибирование окисления ловушек с помощью карнозина указывает на способность карнозина взаимодействовать с 1О2. Кроме того, карнозин снижал интенсивность хемилюминесценции, индуцируемой синглетным кислородом, образующимся в смеси Н2О2+NaClO, подтверждая способность тушить 1О2 ADDIN EN.CITE <EndNote><Cite><Author>Швачко</Author><Year>1990</Year><RecNum>166</RecNum><DisplayText>[213]</DisplayText><record><rec-number>166</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">166</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" charset="204" size="100%">Швачко,</style><style face="normal" font="default" size="100%"> </style><style face="normal" font="default" charset="204" size="100%">А.Г., Формазюк, В.Е., Сергиенко В.И.</style></author></authors></contributors><titles><title><style face="normal" font="default" charset="204" size="100%">Тушение хемилюминесценции синглетного кислорода в присутствии карнозина</style></title></titles><pages><style face="normal" font="default" charset="204" size="100%">155-156</style></pages><dates><year><style face="normal" font="default" charset="204" size="100%">1990</style></year></dates><urls></urls></record></Cite></EndNote>[213]. Интересно отметить, что при эквимолярных концентрациях эффективность тушения 1О2 карнозином была выше, чем у гистидина, известной ловушки для 1О2 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmF3bjwvQXV0aG9yPjxZZWFyPjE5ODE8L1llYXI+PFJl
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ADDIN EN.CITE.DATA [211, 212, 214]. Более высокая эффективность карнозина по сравнению с гистидином, возможно, связана с особенностями внутримолекулярных взаимодействий (влияние -аланина), что приводит к большей реакционной способности гистидина в молекуле карнозина.
Методом синхронной регистрации светопоглощения при радиолизе водного раствора карнозина было выявлено образование комплекса между супероксидом и карнозином с частичным переносом заряда. Образование комплекса приводило к снижению константы скорости дисмутации О2-• и повышению его стабильности в водном растворе ADDIN EN.CITE <EndNote><Cite><Author>Pavlov</Author><Year>1990</Year><RecNum>135</RecNum><DisplayText>[14]</DisplayText><record><rec-number>135</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">135</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pavlov, A. R.</author><author>Revina, A. A.</author><author>Dupin, A. M.</author><author>Boldyrev, A. A.</author><author>Iaropolov, A. I.</author></authors></contributors><titles><title>[Interactions of carnosine and superoxide radicals in aqueous solutions]</title><secondary-title>Biull Eksp Biol Med</secondary-title><alt-title>Biulleten' eksperimental'noi biologii i meditsiny</alt-title></titles><periodical><full-title>Biull Eksp Biol Med</full-title><abbr-1>Biulleten' eksperimental'noi biologii i meditsiny</abbr-1></periodical><alt-periodical><full-title>Biull Eksp Biol Med</full-title><abbr-1>Biulleten' eksperimental'noi biologii i meditsiny</abbr-1></alt-periodical><pages>391-3</pages><volume>110</volume><number>10</number><edition>1990/10/01</edition><keywords><keyword>Carnosine/ chemistry</keyword><keyword>Free Radicals</keyword><keyword>Hydrogen-Ion Concentration</keyword><keyword>Solutions</keyword><keyword>Superoxides/ chemistry</keyword></keywords><dates><year>1990</year><pub-dates><date>Oct</date></pub-dates></dates><orig-pub>Vzaimodeistvie karnozina s superoksidnymi radikalami v vodnykh rastvorov.</orig-pub><isbn>0365-9615 (Print)
0365-9615 (Linking)</isbn><accession-num>2177670</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>rus</language></record></Cite></EndNote>[14]. Способность карнозина взаимодействовать с супероксид анионом была подтверждена в независимой работе Klebanov et al, где карнозин препятствовал восстановлению нитро-голубого тетразолия под действием О2-• образованного в смеси ксантин+ксантиноксидаза ADDIN EN.CITE <EndNote><Cite><Author>Klebanov</Author><Year>1997</Year><RecNum>144</RecNum><DisplayText>[17]</DisplayText><record><rec-number>144</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">144</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Klebanov, G. I.</author><author>Teselkin Yu, O.</author><author>Babenkova, I. V.</author><author>Popov, I. N.</author><author>Levin, G.</author><author>Tyulina, O. V.</author><author>Boldyrev, A. A.</author><author>Vladimirov Yu, A.</author></authors></contributors><auth-address>Russian State Medical University, Moscow, Russia.</auth-address><titles><title>Evidence for a direct interaction of superoxide anion radical with carnosine</title><secondary-title>Biochem Mol Biol Int</secondary-title><alt-title>Biochemistry and molecular biology international</alt-title></titles><periodical><full-title>Biochem Mol Biol Int</full-title><abbr-1>Biochemistry and molecular biology international</abbr-1></periodical><alt-periodical><full-title>Biochem Mol Biol Int</full-title><abbr-1>Biochemistry and molecular biology international</abbr-1></alt-periodical><pages>99-106</pages><volume>43</volume><number>1</number><edition>1997/10/07</edition><keywords><keyword>Carnosine/ metabolism/pharmacology</keyword><keyword>Luminescent Measurements</keyword><keyword>Luminol/metabolism</keyword><keyword>Nitroblue Tetrazolium/metabolism</keyword><keyword>Oxidation-Reduction</keyword><keyword>Superoxides/ metabolism</keyword><keyword>Xanthine Oxidase/metabolism</keyword></keywords><dates><year>1997</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1039-9712 (Print)
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ADDIN EN.CITE.DATA [215].
С помощью метода электронного парамагнитного резонанса (ЭПР) было продемонстрировано, что добавление карнозина к смеси реакции Фентона приводит к формированию продукта способного конкурировать со спиновой ловушкой для OH• - 5,5-диметилпирролин-N-оксидом (DMPO) ADDIN EN.CITE <EndNote><Cite><Author>Chan</Author><Year>1994</Year><RecNum>145</RecNum><DisplayText>[16, 216]</DisplayText><record><rec-number>145</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">145</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chan, W. K. M., </author><author>Decker, E. A., </author><author>Lee, J. B., </author><author>Butterfield, D. A. </author></authors></contributors><titles><title>EPR spin-trapping studies of the hydroxyl radical scavenging activity of carnosine and related dipeptides</title><secondary-title>J Agric Food Chem</secondary-title></titles><periodical><full-title>J Agric Food Chem</full-title><abbr-1>Journal of agricultural and food chemistry</abbr-1></periodical><pages>1407-1410</pages><volume>42</volume><dates><year>1994</year></dates><urls></urls></record></Cite><Cite><Author>RUBTSOV</Author><Year>1991</Year><RecNum>171</RecNum><record><rec-number>171</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">171</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>RUBTSOV, AM</author><author>SCHARA, M.</author><author>SENTJURC, M.</author><author>BOLDYREV, AA</author></authors></contributors><titles><title>HYDROXYL RADICAL-SCAVENGING ACTIVITY OF CARNOSINE - A SPIN TRAPPING STUDY</title><secondary-title>Acta Pharmaceutica Jugoslavika</secondary-title></titles><periodical><full-title>Acta Pharmaceutica Jugoslavika</full-title></periodical><pages>401-407</pages><volume>41</volume><number>4</number><dates><year>1991</year></dates><label>boldyrev1991hydroxyl1978455</label><work-type>journal article</work-type><urls><related-urls><url>http://istina.msu.ru/publications/article/1978455/</url></related-urls></urls></record></Cite></EndNote>[16, 216]. Гистидин и гомокарнозин взаимодействовали с OH• менее эффективно, чем карнозин. Образование комплексов OH• с -аланином и ГАМК обнаружено не было. Интересно отметить, что эффективность связывания OH• в смеси -аланин+гистидин была ниже, чем в присутствии карнозина, что еще раз подтверждает важную роль внутримолекулярных взаимодействий для антиоксидантного эффекта карнозина ADDIN EN.CITE <EndNote><Cite><Author>Chan</Author><Year>1994</Year><RecNum>145</RecNum><DisplayText>[16]</DisplayText><record><rec-number>145</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">145</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chan, W. K. M., </author><author>Decker, E. A., </author><author>Lee, J. B., </author><author>Butterfield, D. A. </author></authors></contributors><titles><title>EPR spin-trapping studies of the hydroxyl radical scavenging activity of carnosine and related dipeptides</title><secondary-title>J Agric Food Chem</secondary-title></titles><periodical><full-title>J Agric Food Chem</full-title><abbr-1>Journal of agricultural and food chemistry</abbr-1></periodical><pages>1407-1410</pages><volume>42</volume><dates><year>1994</year></dates><urls></urls></record></Cite></EndNote>[16].
В ряде работ были продемонстрированы способности карнозина взаимодействовать с продуктами ПОЛ, препятствуя распространению окислительного повреждения. Карнозин сдерживал накопление малонового альдегида, образующегося в результате окисления фрагментов саркоплазматического ретикулума, и способствовал сохранению функций мембран ADDIN EN.CITE <EndNote><Cite><Author>Dupin</Author><Year>1984</Year><RecNum>113</RecNum><DisplayText>[18]</DisplayText><record><rec-number>113</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">113</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dupin, A. M.</author><author>Boldyrev, A. A.</author><author>Arkhipenko Iu, V.</author><author>Kagan, V. E.</author></authors></contributors><titles><title>[Carnosine protection of Ca2+ transport against damage induced by lipid peroxidation]</title><secondary-title>Biull Eksp Biol Med</secondary-title><alt-title>Biulleten' eksperimental'noi biologii i meditsiny</alt-title></titles><periodical><full-title>Biull Eksp Biol Med</full-title><abbr-1>Biulleten' eksperimental'noi biologii i meditsiny</abbr-1></periodical><alt-periodical><full-title>Biull Eksp Biol Med</full-title><abbr-1>Biulleten' eksperimental'noi biologii i meditsiny</abbr-1></alt-periodical><pages>186-8</pages><volume>98</volume><number>8</number><edition>1984/08/01</edition><keywords><keyword>Animals</keyword><keyword>Biological Transport/drug effects</keyword><keyword>Calcium/ metabolism</keyword><keyword>Carnosine/ pharmacology</keyword><keyword>Dipeptides/ pharmacology</keyword><keyword>Lipid Peroxides/ metabolism</keyword><keyword>Muscles/drug effects/metabolism</keyword><keyword>Oxidation-Reduction/drug effects</keyword><keyword>Rana temporaria</keyword><keyword>Sarcoplasmic Reticulum/drug effects/metabolism</keyword></keywords><dates><year>1984</year><pub-dates><date>Aug</date></pub-dates></dates><orig-pub>Zashchita karnozinom transporta Ca2+ ot povrezhdenii, vyzyvaemykh perekisnym okisleniem lipidov.</orig-pub><isbn>0365-9615 (Print)
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ADDIN EN.CITE.DATA [15, 19].
Одним из проявлений антиоксидантных свойств карнозина является его радиомодифицирующий эффект. Повреждающее действие ионизирующего излучения связано, главным образом, с развитием мощнейшего окислительного стресса в результате радиолиза воды. Пероральное введение мышам карнозина в течение 20 суток перед облучением способствовало повышению выживаемости животных ADDIN EN.CITE <EndNote><Cite><Author>Северин С. Е.</Author><Year>1990</Year><RecNum>167</RecNum><DisplayText>[218]</DisplayText><record><rec-number>167</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">167</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" charset="204" size="100%">Северин С. Е., Болдырев А. А., Стволинский С. Л., Бордюков, М.М., Гончаренко, Е.Н., Деев, Л.И., Малинина, И.Е., Кудряшов, Ю.Е. </style></author></authors></contributors><titles><title><style face="normal" font="default" charset="204" size="100%">О радиомодифицирующих свойствах карнозина</style></title><secondary-title><style face="normal" font="default" charset="204" size="100%">Радиобиология</style></secondary-title></titles><periodical><full-title>Радиобиология</full-title></periodical><pages><style face="normal" font="default" charset="204" size="100%">765-768</style></pages><volume><style face="normal" font="default" charset="204" size="100%">30</style></volume><number><style face="normal" font="default" charset="204" size="100%">6</style></number><dates><year><style face="normal" font="default" charset="204" size="100%">1990</style></year></dates><urls></urls></record></Cite></EndNote>[218]. Радиомодифицирующее действие карнозина было подтверждено с помощью метода эндогенных селезеночных колоний. Было обнаружено увеличение эффективности образования колоний гематопоэтическими стволовыми клетками из костного мозга мышей, которым перед облучением вводили карнозин, по сравнению с контрольными животными PEVuZE5vdGU+PENpdGU+PEF1dGhvcj7QmtGD0YDQtdC70LvQsDwvQXV0aG9yPjxZZWFyPjE5OTE8
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ADDIN EN.CITE.DATA [219, 220]. 1.3.3. Эффект карнозина и его производных на пролиферацию нормальных и опухолевых клетокПродолжительное культивирование нормальных человеческих фибробластов с карнозином (10 - 50 мМ) приводило к удлинению продолжительности жизни клеток, что выражалось в увеличении количества популяционных удвоений, т.н. предела Хейфлика ADDIN EN.CITE <EndNote><Cite><Author>Hayflick</Author><Year>1965</Year><RecNum>226</RecNum><DisplayText>[221]</DisplayText><record><rec-number>226</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">226</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hayflick, L.</author></authors></contributors><titles><title>THE LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS</title><secondary-title>Exp Cell Res</secondary-title><alt-title>Experimental cell research</alt-title></titles><periodical><full-title>Exp Cell Res</full-title><abbr-1>Experimental cell research</abbr-1></periodical><alt-periodical><full-title>Exp Cell Res</full-title><abbr-1>Experimental cell research</abbr-1></alt-periodical><pages>614-36</pages><volume>37</volume><edition>1965/03/01</edition><keywords><keyword>Aging</keyword><keyword>Cell Division</keyword><keyword>Chromosome Aberrations</keyword><keyword>Fetus</keyword><keyword>Lung</keyword><keyword>Tissue Culture Techniques</keyword></keywords><dates><year>1965</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0014-4827 (Print)
0014-4827 (Linking)</isbn><accession-num>14315085</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[221]. Кроме того, отмечали задержку развития старческого фенотипа в виде усиления зернистости и потери вытянутой фибробластоподобной формы ADDIN EN.CITE <EndNote><Cite><Author>McFarland</Author><Year>1994</Year><RecNum>162</RecNum><DisplayText>[22]</DisplayText><record><rec-number>162</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">162</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McFarland, G. A.</author><author>Holliday, R.</author></authors></contributors><auth-address>CSIRO Division of Biomolecular Engineering, Sydney Laboratory, NSW, Australia.</auth-address><titles><title>Retardation of the senescence of cultured human diploid fibroblasts by carnosine</title><secondary-title>Exp Cell Res</secondary-title><alt-title>Experimental cell research</alt-title></titles><periodical><full-title>Exp Cell Res</full-title><abbr-1>Experimental cell research</abbr-1></periodical><alt-periodical><full-title>Exp Cell Res</full-title><abbr-1>Experimental cell research</abbr-1></alt-periodical><pages>167-75</pages><volume>212</volume><number>2</number><edition>1994/06/01</edition><keywords><keyword>Carnosine/ pharmacology</keyword><keyword>Cell Aging/ drug effects</keyword><keyword>Fibroblasts</keyword><keyword>Humans</keyword></keywords><dates><year>1994</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0014-4827 (Print)
0014-4827 (Linking)</isbn><accession-num>8187813</accession-num><urls></urls><electronic-resource-num>10.1006/excr.1994.1132</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[22]. Добавление карнозина к клеткам долгое время культивируемым на среде без карнозина приводило к обращению старческого фенотипа и способствовало увеличению продолжительности их жизни в сравнении с контролем. Удаление карнозина из среды нивелировало описанный эффект ADDIN EN.CITE <EndNote><Cite><Author>McFarland</Author><Year>1999</Year><RecNum>161</RecNum><DisplayText>[222]</DisplayText><record><rec-number>161</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">161</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McFarland, G. A.</author><author>Holliday, R.</author></authors></contributors><auth-address>CSIRO Division of Molecular Science, Sydney Laboratory, North Ryde, Australia.</auth-address><titles><title>Further evidence for the rejuvenating effects of the dipeptide L-carnosine on cultured human diploid fibroblasts</title><secondary-title>Exp Gerontol</secondary-title><alt-title>Experimental gerontology</alt-title></titles><periodical><full-title>Exp Gerontol</full-title><abbr-1>Experimental gerontology</abbr-1></periodical><alt-periodical><full-title>Exp Gerontol</full-title><abbr-1>Experimental gerontology</abbr-1></alt-periodical><pages>35-45</pages><volume>34</volume><number>1</number><edition>1999/04/10</edition><keywords><keyword>Carnosine/ pharmacology</keyword><keyword>Cell Adhesion/drug effects</keyword><keyword>Cell Aging/ drug effects</keyword><keyword>Cell Division/drug effects</keyword><keyword>Cells, Cultured</keyword><keyword>Fibroblasts/drug effects/physiology</keyword><keyword>Humans</keyword></keywords><dates><year>1999</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0531-5565 (Print)
0531-5565 (Linking)</isbn><accession-num>10197726</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[222]. Карнозин также способствовал увеличению эффективности посева фибробластов. При посеве клеток в низких разведениях, в чашках инкубируемых с карнозином образовывалось больше колоний, чем в контрольных, что указывает на активацию пролиферативных процессов фибробластов под действием карнозина ADDIN EN.CITE <EndNote><Cite><Author>McFarland</Author><Year>1999</Year><RecNum>161</RecNum><DisplayText>[222]</DisplayText><record><rec-number>161</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">161</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McFarland, G. A.</author><author>Holliday, R.</author></authors></contributors><auth-address>CSIRO Division of Molecular Science, Sydney Laboratory, North Ryde, Australia.</auth-address><titles><title>Further evidence for the rejuvenating effects of the dipeptide L-carnosine on cultured human diploid fibroblasts</title><secondary-title>Exp Gerontol</secondary-title><alt-title>Experimental gerontology</alt-title></titles><periodical><full-title>Exp Gerontol</full-title><abbr-1>Experimental gerontology</abbr-1></periodical><alt-periodical><full-title>Exp Gerontol</full-title><abbr-1>Experimental gerontology</abbr-1></alt-periodical><pages>35-45</pages><volume>34</volume><number>1</number><edition>1999/04/10</edition><keywords><keyword>Carnosine/ pharmacology</keyword><keyword>Cell Adhesion/drug effects</keyword><keyword>Cell Aging/ drug effects</keyword><keyword>Cell Division/drug effects</keyword><keyword>Cells, Cultured</keyword><keyword>Fibroblasts/drug effects/physiology</keyword><keyword>Humans</keyword></keywords><dates><year>1999</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0531-5565 (Print)
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ADDIN EN.CITE.DATA [223]. Укорачивание теломер представляется одним из основных факторов ограничивающий количество клеточных делений ADDIN EN.CITE <EndNote><Cite><Author>Levy</Author><Year>1992</Year><RecNum>227</RecNum><DisplayText>[224]</DisplayText><record><rec-number>227</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">227</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Levy, M. Z.</author><author>Allsopp, R. C.</author><author>Futcher, A. B.</author><author>Greider, C. W.</author><author>Harley, C. B.</author></authors></contributors><auth-address>Department of Biochemistry, McMaster University Hamilton, Ontario, Canada.</auth-address><titles><title>Telomere end-replication problem and cell aging</title><secondary-title>J Mol Biol</secondary-title><alt-title>Journal of molecular biology</alt-title></titles><periodical><full-title>J Mol Biol</full-title><abbr-1>Journal of molecular biology</abbr-1></periodical><alt-periodical><full-title>J Mol Biol</full-title><abbr-1>Journal of molecular biology</abbr-1></alt-periodical><pages>951-60</pages><volume>225</volume><number>4</number><edition>1992/06/20</edition><keywords><keyword>Adult</keyword><keyword>Base Sequence</keyword><keyword>Cell Division</keyword><keyword>Cells, Cultured</keyword><keyword>Chromosome Deletion</keyword><keyword>Chromosomes, Human/ physiology</keyword><keyword>DNA/genetics/ metabolism</keyword><keyword>DNA Replication</keyword><keyword>Fibroblasts/cytology/physiology</keyword><keyword>Humans</keyword><keyword>Kinetics</keyword><keyword>Models, Genetic</keyword><keyword>Oligonucleotide Probes</keyword><keyword>Repetitive Sequences, Nucleic Acid</keyword><keyword>Skin Physiological Phenomena</keyword><keyword>Telomere/ physiology</keyword></keywords><dates><year>1992</year><pub-dates><date>Jun 20</date></pub-dates></dates><isbn>0022-2836 (Print)
0022-2836 (Linking)</isbn><accession-num>1613801</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[224], замедление этого процесса может быть одним из механизмов удлинения предела Хейфлика и задержки формирования старческого фенотипа с помощью карнозина.
В 1986 году, японские ученые Nagai и Suda впервые описали эффект карнозина на опухолевый клетки, который в корне отличался от действия карнозина на нормальные клетки. Подкожные инъекции карнозина мышам линии ddY, которым предварительно вживляли клетки саркомы, способствовали снижению интенсивности пролиферации опухолевых клеток и увеличивали выживаемость животных ADDIN EN.CITE <EndNote><Cite><Author>Nagai</Author><Year>1986</Year><RecNum>88</RecNum><DisplayText>[20]</DisplayText><record><rec-number>88</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">88</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nagai, K.</author><author>Suda, T.</author></authors></contributors><titles><title>[Antineoplastic effects of carnosine and beta-alanine--physiological considerations of its antineoplastic effects]</title><secondary-title>Nihon Seirigaku Zasshi</secondary-title><alt-title>Nihon seirigaku zasshi. Journal of the Physiological Society of Japan</alt-title></titles><periodical><full-title>Nihon Seirigaku Zasshi</full-title><abbr-1>Nihon seirigaku zasshi. Journal of the Physiological Society of Japan</abbr-1></periodical><alt-periodical><full-title>Nihon Seirigaku Zasshi</full-title><abbr-1>Nihon seirigaku zasshi. Journal of the Physiological Society of Japan</abbr-1></alt-periodical><pages>741-7</pages><volume>48</volume><number>11</number><edition>1986/01/01</edition><keywords><keyword>Alanine/ pharmacology</keyword><keyword>Animals</keyword><keyword>Antineoplastic Agents</keyword><keyword>Carnosine/administration & dosage/ pharmacology/therapeutic use</keyword><keyword>Dipeptides/ pharmacology</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mitomycin</keyword><keyword>Mitomycins/administration & dosage</keyword><keyword>Picibanil/administration & dosage</keyword><keyword>Sarcoma 180/drug therapy</keyword><keyword>beta-Alanine/administration & dosage/ pharmacology/therapeutic use</keyword></keywords><dates><year>1986</year></dates><isbn>0031-9341 (Print)
0031-9341 (Linking)</isbn><accession-num>3102721</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>jpn</language></record></Cite></EndNote>[20]. В независимом исследовании Renner et al. на мышах с ксенографами HER2/neu NIH3T3 фибробластов показали, что ежедневные внутрибрюшинные инъекции карнозина существенно подавляют пролиферацию злокачественных клеток и опухолевый рост. Снижение скорости пролиферации опухолевых клеток под действием карнозина сопровождалось снижением синтеза АФК и активности лактатдегидрогеназы (ЛДГ). Кроме того, в опухолях мышей, которым делали инъекции карнозина карнозина было обнаружено меньшее количество митозов, чем у контрольных животных PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SZW5uZXI8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA [21]. Сходные изменения наблюдали в первичной культуре клеток мультиформной глиобластомы (Glioblastoma multiforme). Обработка клеток карнозином (20-50 мМ) в течение 4 дней приводила к уменьшению внутриклеточного уровня АТФ и ЛДГ, а также к снижению синтеза ДНК ADDIN EN.CITE <EndNote><Cite><Author>Renner</Author><Year>2008</Year><RecNum>91</RecNum><DisplayText>[208]</DisplayText><record><rec-number>91</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">91</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Renner, C., Seyffarth, A., Garcia de Arriba, S., Meixensberger, J., Gebhardt, R., Gaunitz, F.</author></authors></contributors><titles><title>Carnosine Inhibits Growth of Cells Isolated from Human Glioblastoma Multiforme</title><secondary-title>International Journal of Peptide Research and Therapeutics </secondary-title></titles><periodical><full-title>International Journal of Peptide Research and Therapeutics</full-title></periodical><pages>127-135</pages><volume>14</volume><section>127</section><dates><year>2008</year></dates><urls></urls></record></Cite></EndNote>[208]. Ингибирование митохондриального дыхания с помощью KCN в клетках обработанных карнозином не влияло на выработку АТФ или выживаемость клеток. Обработка клеток глиобластомы оксаматом – ингибитором ЛДГ – приводила к резкому снижению концентрации АТФ, при этом карнозин приводил к дальнейшему снижению концентрации АТФ. Исходя из полученных данных авторами был сделан вывод о том, что карнозин индуцирует изменения на уровне гликолиза, которые приводят к ингибированию клеточной пролиферации ADDIN EN.CITE <EndNote><Cite><Author>Renner</Author><Year>2010</Year><RecNum>71</RecNum><DisplayText>[225]</DisplayText><record><rec-number>71</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">71</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Renner, C.</author><author>Asperger, A.</author><author>Seyffarth, A.</author><author>Meixensberger, J.</author><author>Gebhardt, R.</author><author>Gaunitz, F.</author></authors></contributors><auth-address>Klinik und Poliklinik fur Neurochirurgie, Medizinische Fakultat der Universitat Leipzig, Leipzig, Germany.</auth-address><titles><title>Carnosine inhibits ATP production in cells from malignant glioma</title><secondary-title>Neurol Res</secondary-title><alt-title>Neurological research</alt-title></titles><periodical><full-title>Neurol Res</full-title><abbr-1>Neurological research</abbr-1></periodical><alt-periodical><full-title>Neurol Res</full-title><abbr-1>Neurological research</abbr-1></alt-periodical><pages>101-5</pages><volume>32</volume><number>1</number><edition>2009/11/17</edition><keywords><keyword>Adenosine Triphosphate/ metabolism</keyword><keyword>Antineoplastic Agents/ pharmacology</keyword><keyword>Carnosine/ pharmacology</keyword><keyword>Cell Line, Tumor</keyword><keyword>Cells, Cultured</keyword><keyword>Glioma/ drug therapy/ metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Glycolysis/drug effects</keyword><keyword>Humans</keyword><keyword>Mitochondria/drug effects/metabolism</keyword><keyword>Organic Chemicals/pharmacology</keyword><keyword>Potassium Cyanide/pharmacology</keyword></keywords><dates><year>2010</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1743-1328 (Electronic)
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ADDIN EN.CITE.DATA [23, 226]. Добавление карнозина к смеси опухолевых клеток (HeLa) и нормальных человеческих фибробластов (MRC-5) приводило к выборочному уничтожению опухолевых HeLa клеток и способствовало удлинению продолжительности жизни фибробластов ADDIN EN.CITE <EndNote><Cite><Author>Holliday</Author><Year>1996</Year><RecNum>73</RecNum><DisplayText>[23]</DisplayText><record><rec-number>73</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">73</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Holliday, R.</author><author>McFarland, G. A.</author></authors></contributors><auth-address>CSIRO Division of Biomolecular Engineering, Sydney Laboratory, NSW, Australia.</auth-address><titles><title>Inhibition of the growth of transformed and neoplastic cells by the dipeptide carnosine</title><secondary-title>Br J Cancer</secondary-title><alt-title>British journal of cancer</alt-title></titles><periodical><full-title>Br J Cancer</full-title><abbr-1>British journal of cancer</abbr-1></periodical><alt-periodical><full-title>Br J Cancer</full-title><abbr-1>British journal of cancer</abbr-1></alt-periodical><pages>966-71</pages><volume>73</volume><number>8</number><edition>1996/04/01</edition><keywords><keyword>Animals</keyword><keyword>Antineoplastic Agents/ pharmacology</keyword><keyword>Carnosine/ pharmacology</keyword><keyword>Cell Line, Transformed</keyword><keyword>Culture Media</keyword><keyword>Glycolysis/drug effects</keyword><keyword>HeLa Cells</keyword><keyword>Humans</keyword><keyword>Pyruvates/metabolism</keyword><keyword>Pyruvic Acid</keyword><keyword>Simian virus 40</keyword><keyword>Tumor Cells, Cultured</keyword></keywords><dates><year>1996</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0007-0920 (Print)
0007-0920 (Linking)</isbn><accession-num>8611433</accession-num><urls></urls><custom2>PMC2075811</custom2><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[23]. Интересно отметить, что действие карнозина на две активно пролиферирующие культуры – эмбриональные стволовые (ЭС) клетки мыши и иммортальные клетки эмбриональной терато-карциномы (ЭК) мыши также было различно. Карнозин препятствовал росту злокачественных ЭК-клеток, не затрагивая роста ЭС-клеток ADDIN EN.CITE <EndNote><Cite><Author>McFarland</Author><Year>1999</Year><RecNum>160</RecNum><DisplayText>[226]</DisplayText><record><rec-number>160</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">160</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McFarland, G.</author><author>Holliday, R.</author></authors></contributors><titles><title>Differential response of embryonic stem cells and teratocarcinoma cells to carnosine</title><secondary-title>In Vitro Cell Dev Biol Anim</secondary-title><alt-title>In vitro cellular & developmental biology. Animal</alt-title></titles><periodical><full-title>In Vitro Cell Dev Biol Anim</full-title><abbr-1>In vitro cellular & developmental biology. Animal</abbr-1></periodical><alt-periodical><full-title>In Vitro Cell Dev Biol Anim</full-title><abbr-1>In vitro cellular & developmental biology. Animal</abbr-1></alt-periodical><pages>15-6</pages><volume>35</volume><number>1</number><edition>1999/09/04</edition><keywords><keyword>Animals</keyword><keyword>Carnosine/ pharmacology</keyword><keyword>Cell Division/drug effects</keyword><keyword>Embryo, Mammalian</keyword><keyword>Mice</keyword><keyword>Stem Cells/ drug effects/metabolism</keyword><keyword>Teratocarcinoma/ metabolism</keyword></keywords><dates><year>1999</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1071-2690 (Print)
1071-2690 (Linking)</isbn><accession-num>10475249</accession-num><urls></urls><electronic-resource-num>10.1007/s11626-999-0037-1</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[226]. Полученные данные указывали на то, что ни степень дифференцировки, ни скорость пролиферации клеток не являются определяющими факторами избирательного действия карнозина на опухолевые клетки.
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ADDIN EN.CITE.DATA [227-230], а BAG2 и GrpEL вовлечены в регуляцию активности белков теплового шока (Heat shock protein 70, Hsp70) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Cb3JnZXM8L0F1dGhvcj48WWVhcj4yMDAzPC9ZZWFyPjxS
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«