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Tubastatin A attenuates chronic angiotensin‐II‐induced autophagy
Author(s) -
Rajasingh Sheeja,
Czirok Andras,
Isai Dona Greta,
Rajasingh Johnson
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.662.33
Subject(s) - autophagy , angiotensin ii , microbiology and biotechnology , chemistry , programmed cell death , apoptosis , atg5 , biology , biochemistry , receptor
It has been shown that autophagy is playing one of the crucial cellular functions, which maintain the cellular homeostasis as well as cardiac hypertrophy, but the mechanism is poorly understood. Studies have shown that over activation of autophagy is not always protective but may cause autophagic cell death. Recent reports have demonstrated that STAT3 participates in the process of autophagy. Bcl2 is an anti‐apoptotic and anti‐autophagic protein that inhibits autophagy through direct interaction with the BH3 domain of pro‐autophagic protein beclin1. Here we have examined the protective role of HDAC6 inhibitor Tubastatin A (TBSA) during chronic angiotensin II‐induced autophagy in human iPSC‐derived cardiomyocytes (hiCMCs). Hypothesis We hypothesize that TBSA treatment mediated activation of STAT3‐Bcl2 is a critical regulator of angiotensin II‐induced hiCMCs autophagy and the over expression of HDAC6 in hiCMCs leads to exaggerate angiotensin II‐induced autophagy. Methods and Results We have evaluated the TBSA treatment mediated effects in the contractility of hiCMCs, cell size and mitochondrial membrane potential in response to angiotensin II‐induced autophagy. Our data shows that the functional effect of hiCMCs stimulated with angiotensin II has significantly reduced the beating frequency, whereas treatment with TBSA rescued the beating frequency (Fig. A, B). Furthermore, the angiotensin II‐induced hypertrophic effect on hiCMCs is significantly reduced by TBSA treatment (Fig. C). Moreover, the immunostaining with JC1 (marker for Autophagy) shows that the mitochondrial membrane potential significantly reduced in angiotensin II‐induced hiCMCs, whereas TBSA treatment maintains the mitochondrial membrane potential (Fig D). Moreover, our electron microscopic analysis revealed a dramatic difference was observed between angiotensin II induced hiCMCs and Angiotensin II‐induced hiCMCs treated with TBSA in actin cytoskeletal protein and disorganized sarcomeres. Conclusions We report for the first time that the role of HDAC6 in regulation of pathological autophagy, thus can acts as a potential therapeutic target for treatment of chronic heart diseases. Support or Funding Information American Heart Association Grant‐in‐Aid Grant 16GRNT30950010 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .