[Frontiers in Bioscience 19, 1355-1369, June 1, 2014]

Regulation of cystathionine gamma-lyase/H2S system and its pathological implication

Kexin Zhao1,2, Hongzhu Li3, Shuangshuang Li1,2, Guangdong Yang1,2

1The Cardiovascular and Metabolic Research Unit, and 2School of Kinesiology, Lakehead University, Thunder Bay, Canada; 3Department of Pathophysiology, Harbin Medical University, Harbin, China


1. Abstract
2. Introduction
3. Abnormal CSE expression and H2S production in both health and diseases
3.1. Cardiovascular diseases
3.2. Diabetes
3.3. Liver and kidney diseases
3.4. Cancer
3.5. Aging
3.6. Asthma
3.7. Others
4. The regulatory mechanisms underlying altered CSE expression and H2S production
4.1. Transcription factor regulation of CSE transcription
4.2. MicroRNA regulation of CSE protein translation
4.3. PLP regulation of CSE activity
4.4. Key residues involved in the catalysis of H2S
4.5. Hormone regulation of CSE activity
4.6. Calcium regulation of CSE activity
4.7. NO and CO regulation of CSE activity
4.8. CSE inhibitors
5. Perspective
6. Acknowledgements
7. References


Hydrogen sulfide (H2S) is a highly diffusible gasotransmitter, that influence cellular and organ functions by a number of different mechanisms. Cystathionine gamma-lyase (CSE) is one major H2S-producing enzyme with L-cysteine as the main substrate in mammalian cells. Since the discovery of endogenously-produced H2S as a biological mediator, there has been an explosion of interest in CSE expression and regulation. CSE expression and activity and ultimately the amount of H2S synthesis is controlled by a complex integration of transcriptional, post-transcriptional and post-translational mechanisms. Considering the key role that CSE/H2S system plays in both health and diseases, a better understanding of the regulation of CSE/H2S system will help us to develop novel and more effective strategies to target CSE and alter H2S production inside cells. In this review, we summarize the altered expression and activity of CSE and abnormal H2S production in various pathophysiological conditions. The current knowledge on the signaling and regulatory pathways for CSE expression and H2S production are also elucidated. As such, our understanding of the pathogenesis of human diseases will be better achieved and the corresponding new therapy can be devised.