Decreased α-tubulin acetylation induced by an acidic environment impairs autophagosome formation and leads to rat cardiomyocyte injury.

Extracellular pH strongly affects cellular metabolism and function. An acidic environment induced under pathological conditions leads to cardiomyocyte injury and dysfunction, but the underlying mechanisms are still poorly understood. Autophagy has been reported as a cytoprotective mechanism that maintains cellular metabolism and viability by removing misfolded proteins and damaged organelles. In our research, we found that acidic environments inhibit autophagosome formation in cardiomyocytes. Up-regulation of autophagic activity, however, ameliorates the cell injury induced by acidic treatments.We also found that acidic treatments reduce the level of α-tubulin acetylation, as detected by Western blot and immunofluorescence staining, and that the number of autophagosomes increase after up-regulating α-tubulin acetylation by Taxol, suggesting that α-tubulin acetylation may play an important role in acidic pH-induced changes in autophagy. Furthermore, an HDAC6 activity assay showed an increase in HDAC6 activity after acidic treatment and that inhibiting HDAC6 activity by tubastatin A or specific siRNA up-regulates α-tubulin acetylation and autophagosome formation. These data confirm that autophagy plays a protective role against acidic pH-induced cell injury and indicate that HDAC6-mediated α-tubulin acetylation is an important mechanism of acidic pH-dependent autophagy in cardiomyocytes.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}