Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC56610.15690/vramn566РATHOPHYSIOLOGY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ПАТОФИЗИОЛОГИИLigands of RAGE-Proteins: Role in Intercellular Communication and Pathogenesis of InflammationЛиганды RAGE-белков: роль в межклеточной коммуникации и патогенезе воспаленияUspenskayaYuliya AleksandrovnaУспенскаяЮлия Александровна
Russian Federation

доктор биологических наук, научный сотрудник НИИ молекулярной медицины и патобиохимии

uspenskaya.yulia@gmail.comKomlevaYuliya KonstantinovnaКомлеваЮлия Константиновна
Russian Federation

кандидат медицинских наук, доцент кафедры биохимии с курсами медицинской, фармацевтической и токсикологической химии, научный сотрудник НИИ молекулярной медицины и патобиохимии

yuliakomleva@mail.ruPozhilenkovaElena Anatol'evnaПожиленковаЕлена Анатольевна
Russian Federation

кандидат биологических наук, доцент кафедры биохимии с курсами медицинской, фармацевтической и токсикологической химии, исполнительный директор НИИ молекулярной медицины и патобиохимии

Elena.a.pozhilenkova@gmail.comSalminVladimir Valer'evicСалминВладимир Валерьевич
Russian Federation

доктор физико-математических наук, зав. кафедрой медицинской и биологической физики

vsalmin@gmail.comLopatinaOl'ga LeonidovnaЛопатинаОльга Леонидовна
Russian Federation

кандидат биологических наук, доцент кафедры биохимии с курсами медицинской, фармацевтической и токсикологической химии, научный сотрудник НИИ молекулярной медицины и патобиохимии

ol.lopatina@gmail.comFursovAleksandr Anatol'evichФурсовАлександр Анатольевич
Russian Federation

кандидат медицинских наук, ассистент кафедры анестезиологии и реаниматологии Института последипломного образования

fursov_alex@mail.ruLavrent'evPavel VyacheslavovichЛаврентьевПавел Вячеславович
Russian Federation

преподаватель кафедры медицинской и биологической физики, научный сотрудник НИИ молекулярной медицины и патобиохимии

lavran@inbox.ruBelovaOl'ga Anatol'evnaБеловаОльга Анатольевна
Russian Federation

ассистент кафедры травматологии, ортопедии и ВПХ с курсом ПО им. проф. Л.Л. Роднянского

ulyabelova@mail.ruSalminaAlla BorisovnaСалминаАлла Борисовна
Russian Federation

доктор медицинских наук, профессор, зав. кафедрой биохимии с курсами медицинской, фармацевтической и токсикологической химии, руководитель НИИ молекулярной медицины и патобиохимии

allasalmina@mail.ruKrasnoyarsk State Medical UniversityГБОУ ВПО «Красноярский государственный медицинский университет имени профессора В.Ф. Войно-Ясенецкого» Минздрава России311220157066947030812201508122015Copyright ©; 2015, "Paediatrician" Publishers LLCCopyright ©; 2015, Издательство "Педиатръ"2015"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/566

The review contains data on the diversity of endogenous ligands of RAGE receptors (receptor for advanced glycation end products) that play an important role in the signal transduction in (patho) physiological conditions. RAGE takes part in various physiological processes like cell growth and survival, apoptosis and regeneration. They serve as regulators of inflammatory reactions due to their ability to induce secretion of cytokines and chemokines. In addition, they facilitate elimination of apoptotic cells and mediate innate immune response. We discuss mechanisms of soluble RAGE production as well as the role of membrane and soluble forms of the receptor in cell signaling. Several endogenous ligands of RAGE are well-known: advanced glycation end products (AGE), amyloid-beta (Аβ), nuclear high mobility group box 1 proteins (HMGB1), and calcium-binding proteins S100A4, S100A8/A9, S100A12 и S100B. The review is focused on the mechanisms of the ligands production, their secretion from the cells of various origin, interaction with RAGE, and associated intracellular signal transduction pathways. Special attention is paid to the role of RAGE in pathogenesis of inflammation, particularly, in brain injury and neurodegeneration.

В обзоре литературы обсуждается разнообразие эндогенных лигандов RAGE-рецепторов, играющих важную роль в сигнальной трансдукции в физиологических условиях и при патологии. RAGE-рецепторы опосредуют многие физиологические функции, такие как рост клеток, апоптоз, выживание и регенерация; участвуют в воспалительных реакциях, индуцируя секрецию цитокинов и хемокинов; способствуют элиминации апоптотических клеток, являются участниками врожденного иммунного ответа. Рассмотрены механизмы образования растворимых форм RAGE, а также роль мембранной и растворимой форм рецепторов в передаче сигнальной информации при активации клеток. Признанными лигандами RAGE являются продукты неферментативного гликирования белков, бета-амилоид, ядерные белки HMGB1, кальцийсвязывающие белки S100A4, S100A8/A9, S100A12 и S100B. В статье обсуждаются механизмы продукции лигандов RAGE, секреции их из клеток различной природы, их взаимодействие с рецепторами и последствия этого взаимодействия для клеток и тканей. Особое внимание уделено анализу роли лигандов RAGE в развитии воспаления, в частности при повреждении головного мозга и нейродегенерации.

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