Heart failure results from the heart's inability to carryout ventricular contraction and relaxation, and has now become a worldwide problem. During the onset of heart failure, several signatures are observed in cardiomyocytes that includes fetal reprogramming of gene expression where adult genes are repressed and fetal genes turned on, endoplasmic reticulum stress and oxidative stress. In this short review and analysis, we examine these different phenomenon from the viewpoint of the glutathione cycle and the role of the recently discovered Chac1 enzyme. Chac1, which belongs to the family of γ-glutamylcyclotransferases, is a recently discovered member of the glutathione cycle, being involved in the cytosolic degradation of glutathione. This enzyme is induced during the Endoplasmic Stress response, but also in the developing heart. Owing to its exclusive action on reduced glutathione, its induction leads to an increase in the oxidative redox potential of the cell that also serves as signaling mechanism for calcium ions channel activation. The end product of Chac1 action is 5-oxoproline, and studies with 5-oxoprolinase (OPLAH), an enzyme of the glutathione cycle has revealed that down-regulation of OPLAH can lead to the accumulation of 5-oxproline which is an important factor in heart failure. With these recent findings, we have re-examined the roles and regulation of the enzymes in the glutathione cycle which are central to these responses. We present an integrated view of the glutathione cycle in the cellular response to heart failure.
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September 2020
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Cover Image
Cover Image
The cover image is of a molecularly modelled receptor heterodimeric complex in its ligand bound active state (left), juxtaposed to uncomplexed receptors (right) in the presence of the proof of concept inhibitor which prevents ligand bound complex formation. For more information, see the article by Colomba and colleagues (pp. 3329–3347). The image was created by Phospho Biomedical Animation and provided by Peter Parker.
Review Article|
September 04 2020
Heart failure and the glutathione cycle: an integrated view
Anand K. Bachhawat
;
Department of Biological Sciences, Indian Institute of Science Education and Research, Mohali, S.A.S. Nagar, Punjab 140306, India
Correspondence: Anand Kumar Bachhawat (anand@iisermohali.ac.in)
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Shambhu Yadav;
Shambhu Yadav
*
Department of Biological Sciences, Indian Institute of Science Education and Research, Mohali, S.A.S. Nagar, Punjab 140306, India
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Ashwin K. Jainarayanan;
Ashwin K. Jainarayanan
†
Department of Biological Sciences, Indian Institute of Science Education and Research, Mohali, S.A.S. Nagar, Punjab 140306, India
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Pratiksha Dubey
Pratiksha Dubey
Department of Biological Sciences, Indian Institute of Science Education and Research, Mohali, S.A.S. Nagar, Punjab 140306, India
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Publisher: Portland Press Ltd
Received:
May 22 2020
Revision Received:
August 07 2020
Accepted:
August 11 2020
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem J (2020) 477 (17): 3123–3130.
Article history
Received:
May 22 2020
Revision Received:
August 07 2020
Accepted:
August 11 2020
Citation
Anand K. Bachhawat, Shambhu Yadav, Ashwin K. Jainarayanan, Pratiksha Dubey; Heart failure and the glutathione cycle: an integrated view. Biochem J 18 September 2020; 477 (17): 3123–3130. doi: https://doi.org/10.1042/BCJ20200429
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