Heart failure and the glutathione cycle: an integrated view

Abstract

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.

Glutathione Participation in the Prevention of Cardiovascular Diseases

“…Cardiovascular diseases, as occlusion of the coronary arteries, hypertensive heart diseases and strokes, arterial hypertension, myocardial infarction, cerebrovascular disease, heart failure, rheumatic heart disease, congenital heart disease and cardiomyopathies generate thousands of patients with a high mortality and morbidity rates worldwide [ 1 , 2 , 3 , 4 ]. The appearance of these diseases increases with the aging of the population [ 5 , 6 ].…”

CHAC1 as a Novel Contributor of Ferroptosis in Retinal Pigment Epithelial Cells with Oxidative Damage

“…As a component of the unfolded protein response (UPR) pathway, Chac1 is known to be a candidate gene for the glutathione-metabolism-signaling pathway, which accelerates glutathione degradation. Considering that glutathione is a crucial intracellular antioxidant, several studies showed that the dysregulation of Chac1 alters intracellular glutathione expression and is associated with various diseases, such as cancer [ 33 ] and heart failure [ 34 ]. Meanwhile, the silencing of Chac1 has recently been found to ameliorate heat stress (HS)-induced intestinal porcine epithelial cell apoptosis due to the upregulation of glutathione, thereby relieving HS-related intestine impairment [ 35 ].…”

Multi-Omics Analysis of Anti-Inflammatory Action of Alkaline Extract of the Leaves of Sasa sp.

“…This is consistent with our previous finding that Met-sulfoxide and 5-oxoproline declined during the aggravation of IL1-β-induced HGF inflammation by TiO 2 nanoparticles ( Supplementary Figure S2A,B , cited from [ 15 ]). Since Met-sulfoxide [ 23 , 24 , 25 ] and 5-oxoproline [ 26 , 27 , 28 ] are well-known markers reflecting oxidative stress, SE might have induced the cells to fight against oxidative stress.…”