P2Y1 and P2Y2 receptors differ in their role in the regulation of signaling pathways during unloading-induced rat soleus muscle atrophy

This study revealed several key findings following three days of soleus muscle unloading: 1: Inhibition of P2Y1 or P2Y2 receptors prevented the accumulation of ATP, the increase in IP3 receptor content, and the decrease in the phosphorylation of GSK-3beta. This inhibition also mitigated the reduction in the rate of protein synthesis. However, it had no significant effect on the markers of mTORC1-dependent signaling. 2: Blocking P2Y1 receptors prevented the unloading-induced upregulation of phosphorylated p38MAPK and partially reduced the increase in MuRF1mRNA expression. 3: Blocking P2Y2 receptors prevented muscle atrophy during unloading, partially maintained the levels of phosphorylated ERK1/2, reduced the increase in mRNA expression of MAFbx, ubiquitin, and IL-6 receptor, prevented the decrease in phosphorylated AMPK, and attenuated the increase in phosphorylated p70S6K. Taken together, these results suggest that the prevention of muscle atrophy during unloading, as achieved by the P2Y2 receptor inhibitor, is likely mediated through a reduction in catabolic processes and maintenance of energy homeostasis. In contrast, the P2Y1 receptor appears to play a relatively minor role in muscle atrophy during unloading.PMID:38043889 | DOI:10.1016/j.abb.2023.109844

Source: Archives of Biochemistry and Biophysics - December 3, 2023 Category: Biochemistry Authors: Ksenia A Zaripova Svetlana P Belova Tatiana Y Kostrominova Boris S Shenkman Tatiana L Nemirovskaya Source Type: research