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.

中文翻译：

---

心力衰竭和谷胱甘肽循环：综合观点。

心力衰竭是由心脏无法进行心室收缩和舒张引起的，现已成为世界性的问题。在心力衰竭发作期间，在心肌细胞中观察到几个特征，包括胎儿基因表达的重编程，其中成年基因被抑制并且胎儿基因被打开，内质网应激和氧化应激。在简短的回顾和分析中，我们从谷胱甘肽循环和最近发现的Chac1酶的作用的角度研究了这些不同的现象。Chac1，属于γ-谷氨酰环转移酶家族，是最近发现的谷胱甘肽循环成员，参与谷胱甘肽的胞质降解。这种酶在内质应激反应期间以及在发育中的心脏中被诱导。由于其对还原型谷胱甘肽具有排他性作用，其诱导导致细胞氧化氧化还原电位的增加，这也可作为钙离子通道激活的信号传导机制。Chac1作用的最终产物是5-氧代脯氨酸，用谷胱甘肽循环酶5-氧代脯氨酸酶（OPLAH）进行的研究表明，OPLAH的下调可导致5-氧代脯氨酸的积累，这是肝细胞癌的重要因素。心脏衰竭。有了这些最新发现，我们已经重新检查了酶在谷胱甘肽循环中的作用和调节，而这些作用和调节是这些反应的核心。我们提出了对心力衰竭的细胞反应中谷胱甘肽周期的综合看法。它的诱导导致细胞氧化氧化还原电位的增加，这也充当了钙离子通道激活的信号传导机制。Chac1作用的最终产物是5-氧代脯氨酸，用谷胱甘肽循环酶5-氧代脯氨酸酶（OPLAH）进行的研究表明，OPLAH的下调可导致5-氧代脯氨酸的积累，而这是影响心脏衰竭。有了这些最新发现，我们已经重新检查了酶在谷胱甘肽循环中的作用和调节，而这些作用和调节是这些反应的核心。我们提出了对心力衰竭的细胞反应中谷胱甘肽周期的综合看法。它的诱导导致细胞氧化还原电位的增加，这也可以作为钙离子通道激活的信号传导机制。Chac1作用的最终产物是5-氧代脯氨酸，用谷胱甘肽循环酶5-氧代脯氨酸酶（OPLAH）进行的研究表明，OPLAH的下调可导致5-氧代脯氨酸的积累，而这是影响心脏衰竭。有了这些最新发现，我们已经重新审查了谷胱甘肽循环中酶的作用和调节，这些酶和谷氨酸循环对这些反应至关重要。我们提出了对心力衰竭的细胞反应中谷胱甘肽周期的综合看法。谷胱甘肽循环的一种酶显示，OPLAH的下调可导致5-羟脯氨酸的积累，这是心力衰竭的重要因素。有了这些最新发现，我们已经重新审查了谷胱甘肽循环中酶的作用和调节，这些酶和谷氨酸循环对这些反应至关重要。我们提出了对心力衰竭的细胞反应中谷胱甘肽周期的综合看法。谷胱甘肽循环的一种酶显示，OPLAH的下调可导致5-羟脯氨酸的积累，这是心力衰竭的重要因素。有了这些最新发现，我们已经重新检查了酶在谷胱甘肽循环中的作用和调节，而这些作用和调节是这些反应的核心。我们提出了对心力衰竭的细胞反应中谷胱甘肽周期的综合看法。