Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences65174710.31857/S0869813924090084AJUMSNEXPERIMENTAL ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИResearch Article2-APB prevents atrophic changes and alters cellular signalling during unloading of rat M. Soleus2-APB предотвращает атрофические изменения и меняет клеточный сигналинг при функциональной разгрузке M. Soleus крысZaripovaK. A.ЗариповаК. А.
Russian Federation
Nemirovskaya@bk.ruBokovR. O.БоковР. О.
Russian Federation
Nemirovskaya@bk.ruSharloK. A.ШарлоК. А.
Russian Federation
Nemirovskaya@bk.ruBelovaS. P.БеловаС. П.
Russian Federation
Nemirovskaya@bk.ruNemirovskayaT. L.НемировскаяТ. Л.
Russian Federation
Nemirovskaya@bk.ruInstitute of Biomedical Problems RASИнститут медико-биологических проблем РАН1509202411091390140502022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0869-8139/article/view/651747

IP3 receptors are found in significant quantities in muscle fibers in the sarcoplasmic reticulum, nucleus and mitochondria. We hypothesized that activation of IP3 receptors (IP3Rs) during muscle unloading may induce a weak calcium release signal, both cytosolic and nucleoplasmic, that promotes (possibly with other signaling cascades) the activation of transcription factors, leading to the expression or repression of genes involved in muscle phenotype. This hypothesis was tested by blocking IP3R during unloading of rat muscles by administering 2-APB (2-aminoethoxydiphenyl borate). Wistar rats were administered intraperitoneally at a dose of 10 mg/mg in 5 % DMSO daily. We found that the IP3R state influences the development of atrophic processes in the postural m. soleus during unloading. Administration of the IP3R blocker 2-APB to animals successfully prevented a decrease in m. soleus cross-sectional area (CSA) of both fast and slow muscle fibers. The slowdown in CSA decrease upon administration IP3R inhibitor during 7 days m. soleus unloading is associated with the prevention of a decrease in ribosomal biogenesis and an increase in the expression of autophagy markers ULK-1 and IL-6.

IP3-рецепторы (IP3R) находятся в значительном количестве в мышечных волокнах в саркоплазматическом ретикулуме, ядре и митохондриях. Мы предположили, что активация IP3R при разгрузке мышц может вызывать слабый сигнал высвобождения кальция как цитозольный, так и нуклеоплазматический, который способствует (возможно, с другими сигнальными каскадами) активации транскрипционных факторов, что приводит к экспрессии или репрессии генов, участвующих в фенотипе мышц. Эту гипотезу проверяли, применив блокирование IP3R во время функциональной разгрузки мышц крыс путем введения 2-APB (2-aminoethoxydiphenyl borate). Мы обнаружили, что состояние IP3R влияет на развитие атрофических процессов постуральной m. soleus при вывешивании крыс. Введение блокатора IP3R2-APB животным успешно предотвращало снижение площади поперечного сечения m. soleus как быстрых, так и медленных мышечных волокон. Замедление снижения площади поперечного сечения мышечных волокон m. soleus при введении ингибитора IP3R на фоне 7-суточной функциональной разгрузки связано с предотвращением снижения рибосомального биогенеза и повышения экспрессии маркера аутофагии ULK-1 и IL-6.

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