Activation of G alpha(q) in Cardiomyocytes Increases Vps34 Activity and Stimulates Autophagy

作者：Liu Shengnan; Jiang Ya Ping; Ballou Lisa M; Zong Wei Xing; Lin Richard Z^*

来源：Journal of Cardiovascular Pharmacology, 2017, 69(4): 198-211.

DOI：10.1097/FJC.0000000000000461

• G alpha(q)
• autophagy
• heart failure
• electron microscopy
• Vps34 activity
• p62 aggregation

Receptors that activate the heterotrimeric G protein G alpha(q) are thought to play a role in the development of heart failure. Dysregulation of autophagy occurs in some pathological cardiac conditions including heart failure, but whether Gaq is involved in this process is unknown. We used a cardiomyocyte-specific transgenic mouse model of inducible Gaq activation (termed G alpha(q)Q209L) to address this question. After 7 days of Gaq activation, G alpha(q)Q209L hearts contained more autophagic vacuoles than wild type hearts. Increased levels of proteins involved in autophagy, especially p62 and LC3-II, were also seen. LysoTracker staining and western blotting showed that the number and size of lysosomes and lysosomal protein levels were increased in G alpha(q)Q209L hearts, indicating enhanced lysosomal degradation activity. Importantly, an autophagic flux assay measuring LC3-II turnover in isolated adult cardiomyocytes indicated that autophagic activity is enhanced in G alpha(q)Q209L hearts. G alpha(q)Q209L hearts exhibited elevated levels of the autophagy initiation complex, which contains the Class III phosphoinositide 3-kinase Vps34. As a consequence, Vps34 activity and phosphatidylinositol 3-phosphate levels were higher in G alpha(q)Q209L hearts than wild type hearts, thus accounting for the higher abundance of autophagic vacuoles. These results indicate that an increase in autophagy is an early response to Gaq activation in the heart.

• 出版日期2017-4
• 单位rutgers