L-cysteine stimulates hydrogen sulfide synthesis in myocardium associated with attenuation of ischemia-reperfusion injury

Elsey, David, Fowkes, Robert C. and Baxter, Gary Francis ORCID: https://orcid.org/0000-0002-7887-6841 2010. L-cysteine stimulates hydrogen sulfide synthesis in myocardium associated with attenuation of ischemia-reperfusion injury. Journal of Cardiovascular Pharmacology and Therapeutics 15 (1) , pp. 53-59. 10.1177/1074248409357743

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Abstract

Hydrogen sulfide (H 2S) is a biological mediator produced by enzyme-regulated pathways from L-cysteine, which is a substrate for cystathionine-γ-lyase (CSE). In myocardium, endogenously and exogenously administered H2S has been shown to protect against ischemia-reperfusion injury. We hypothesized that L-cysteine exerts its protective action through stimulation of H2S production. Rat isolated hearts were Langendorff-perfused and underwent 35-minute regional ischemia and 120-minute reperfusion. L-cysteine perfusion from 10 minutes before ischemia until 10 minutes after reperfusion limited infarct size in a concentration-dependent manner, maximal at 1 mmol/L (control 36.4% ± 2.4% vs L-cysteine 24.3% ± 3.4%, P < .05). This protective action was attenuated by the CSE inhibitor, DL-propargylglycine (PAG) 1 mmol/L (31.4 ± 5.9%, not significant vs control) but administration of the CSE cofactor pyridoxal-5′-phosphate (PLP) 50 μmol/L did not enhance the effect of L-cysteine. Ten minutes normoxic perfusion with L-cysteine 1 mmol/L caused a 3-fold increase in myocardial H2S concentration (0.64 ± 0.16 vs 2.01 ± 0.07 μmol/g protein, P < .01), an effect that was significantly attenuated by PAG (1.17 ± 0.15 μmol/g protein). These data provide evidence that exogenous L-cysteine administration limits ischemia-reperfusion injury through a mechanism that appears to be at least partially dependent on H2S synthesis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Publisher:	Elsevier
ISSN:	1074-2484
Last Modified:	17 Oct 2022 10:00
URI:	https://orca.cardiff.ac.uk/id/eprint/6510

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