L-Cysteine Stimulates Hydrogen Sulfide Synthesis in Myocardium Associated With Attenuation of Ischemia-Reperfusion Injury

Abstract

Hydrogen sulfide (H( 2)S) is a biological mediator produced by enzyme-regulated pathways from L-cysteine, which is a substrate for cystathionine-gamma-lyase (CSE). In myocardium, endogenously and exogenously administered H(2)S has been shown to protect against ischemia-reperfusion injury. We hypothesized that L-cysteine exerts its protective action through stimulation of H(2)S 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 mumol/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 H(2)S concentration (0.64 +/- 0.16 vs 2.01 +/- 0.07 mumol/g protein, P < .01), an effect that was significantly attenuated by PAG (1.17 +/- 0.15 mumol/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 H(2)S synthesis.

Hydrogen sulfide and hypoxia-induced changes in TASK (K2P3/9) activity and intracellular Ca2+ concentration in rat carotid body glomus cells

“…L-cysteine has been used to increase the endogenous production of H 2 S in a variety of cell types (Elsey et al, 2010; Kaneko et al, 2006; Olson et al, 2008). To test the effect of L-cysteine on TASK activity, glomus cells were incubated in perfusion solution containing 10 mM L-cysteine, and cell-attached patches were formed in the continuous presence of L-cysteine.…”

The therapeutic potential of hydrogen sulfide: separating hype from hope

“…At times, the findings are contradictory, but nevertheless, many are suggestive of therapeutic potential. H 2 S has been shown to be both proinflammatory and anti-inflammatory, to reduce leukocyte adhesion, to inhibit platelet aggregation, and although it is proangiogenic, to reduce deleterious vascular remodeling that often accompanies vascular damage (35,89,155). H 2 S is not only a mild antioxidant, but it also stimulates cysteine uptake and synthesis of glutathione.…”

The role of gasotransmitters NO, H2S and CO in myocardial ischaemia/reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning

“…In rat isolated hearts, infarct size increased when endogenous H2S production was inhibited by blocking CSE with PRG (Bliksoen et al, 2008). In the same experimental model, exogenous L-cysteine administration limited I/R injury through a mechanism that appeared to be at least partially dependent upon H2S synthesis and production was attenuated by PRG treatment (Elsey et al, 2010). Additionally, the modulation of endogenously produced H2S by cardiac-specific overexpression of CSE significantly limited the extent of injury (Elrod et al, 2007).…”