Alcohol Dehydrogenase Protects against Endoplasmic Reticulum Stress-Induced Myocardial Contractile Dysfunction via Attenuation of Oxidative Stress and Autophagy: Role of PTEN-Akt-mTOR Signaling

摘要: Background The endoplasmic reticulum (ER) plays an essential role in ensuring proper folding of the newly synthesized proteins. Aberrant ER homeostasis triggers stress and development cardiovascular diseases. ADH is involved catalyzing ethanol to acetaldehyde although its diseases other than metabolism still remains elusive. This study was designed examine impact on stress-induced cardiac anomalies underlying mechanisms using cardiac-specific overexpression alcohol dehydrogenase (ADH). Methods wild-type FVB mice were subjected inducer tunicamycin (1 mg/kg, i.p., for 48 hrs). Myocardial mechanical intracellular Ca(2+) properties, stress, autophagy associated cell signaling molecules evaluated. Results compromised contractile function (evidenced as reduced fractional shortening, peak maximal velocity shortening/relengthening, prolonged relengthening duration impaired homeostasis), oxidative upregulated (increased LC3B, Atg5, Atg7 p62), along with dephosphorylation PTEN, Akt mTOR, all which attenuated by ADH. In vitro revealed that cardiomyocyte anomaly abrogated or inhibition 3-MA. Interestingly, beneficial effect obliterated induction, mTOR. also promoted phosphorylation ERK JNK, unaffected transgene. Conclusions Taken together, these findings suggested protects against possibly via attenuation PTEN/Akt/mTOR pathway-regulated autophagy.