Autophagy reduction has been confirmed as an important mechanism in apoptosis induction.Our previous study showed that decreased autophagy induced by β1-adrenoceptor autoantibodies (β1-AAs) enhanced cardiomyocyte apoptosis and contributed to heart failure progression.Endoplasmic reticulum stress (ERS) is known to be an important mechanism in intracellular homeostasis and is closely related to autophagy.However,ERS in β1-AA-induced autophagy dysfunction of cardiomyocytes remains unclear.In this study,we used an active immunization rat model and H9c2 cardiomyocytes to study the role of ERS in β1-AA-induced autophagy.Results showed that prolonged action of β1-AAs significantly reduced the autophagy of myocardial tissues and H9c2 cardiomyocytes,and ERS and its related apoptotic pathways were significantly activated.Moreover,mRFP-GFP-LC3 double-labeled adenoviruses were used to detect cardiomyocyte autophagic flux to confirm that β1-AAs caused a significant decrease in autophagic flux in H9c2 cardiomyocytes.The ERS inhibitor,4-phenylbutyrate (4-PBA),partially attenuated the β1-AA-induced reduction of cardiomyocyte autophagy,consistent with the effect of the mammalian target of rapamycin inhibitor rapamycin (Rapa).Compared to the pretreatment with 4-PBA or Rapa alone,pretreatment with the combination of 4-PBA and Rapa had a greater effect on attenuating the β1-AA-induced decrease in autophagy and β1-AA-induced apoptosis in cardiomyocytes.This study provides an experimental basis for the role of β1-AAs in the homeostatic maintenance of cardiomyocytes in patients with heart failure with respect to autophagy and ERS.
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