期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 171, 期 8, 页码 2123-2146出版社
WILEY
DOI: 10.1111/bph.12368
关键词
mitochondrial electron transport; bioenergetics; 3-mercaptopyruvate sulfurtransferase; gasotransmitters; blood vessels; nitric oxide; superoxide; free radicals; cysteine; ischaemia; shock; suspended animation
资金
- National Institutes of Health [P50GM060338]
- Shriners Burns Hospitals [8661]
- American Diabetes Association [7-12-BS-184]
- John Sealy Memorial Endowment Fund for Biomedical Research
- Deutsche Forschungsgemeinschaft [Klinische Forschergruppe 200]
- Land Baden-Wurttemberg (Innovationsfond Medizin)
- Dutch Kidney Foundation [C08-2254]
- COST Action (European Network of Gasotransmitters) [BM1005]
Emerging work demonstrates the dual regulation of mitochondrial function by hydrogen sulfide (H2S), including, at lower concentrations, a stimulatory effect as an electron donor, and, at higher concentrations, an inhibitory effect on cytochrome C oxidase. In the current article, we overview the pathophysiological and therapeutic aspects of these processes. During cellular hypoxia/acidosis, the inhibitory effect of H2S on complex IV is enhanced, which may shift the balance of H2S from protective to deleterious. Several pathophysiological conditions are associated with an overproduction of H2S (e.g. sepsis), while in other disease states H2S levels and H2S bioavailability are reduced and its therapeutic replacement is warranted (e.g. diabetic vascular complications). Moreover, recent studies demonstrate that colorectal cancer cells up-regulate the H2S-producing enzyme cystathionine -synthase (CBS), and utilize its product, H2S, as a metabolic fuel and tumour-cell survival factor; pharmacological CBS inhibition or genetic CBS silencing suppresses cancer cell bioenergetics and suppresses cell proliferation and cell chemotaxis. In the last chapter of the current article, we overview the field of H2S-induced therapeutic suspended animation', a concept in which a temporary pharmacological reduction in cell metabolism is achieved, producing a decreased oxygen demand for the experimental therapy of critical illness and/or organ transplantation. Linked ArticlesThis article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit
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