Whole tissue hydrogen sulfide concentrations are orders of magnitude lower than presently accepted values
Tóm tắt
Hydrogen sulfide is gaining acceptance as an endogenously produced modulator of tissue function. The present paradigm of H2S (diprotonated, gaseous form of hydrogen sulfide) as a tissue messenger consists of H2S being released from the desulfhydration of l-cysteine at a rate sufficient to maintain whole tissue hydrogen sulfide concentrations of 30 μM to >100 μM, and these tissue concentrations serve a messenger function. Utilizing physiological concentrations of l-cysteine and aerobic conditions, we found that catabolism of hydrogen sulfide by mouse liver and brain homogenates exceeded the rate of enzymatic release of this compound such that measureable hydrogen sulfide release was less with tissue-containing vs. tissue-free buffers. Analyses of the gas space over rapidly homogenized mouse brain and liver indicated that in situ tissue hydrogen sulfide concentrations were only about 15 nM. Human alveolar air measurements indicated negligible free H2S concentrations in blood. We conclude rapid tissue catabolism of hydrogen sulfide maintains whole tissue brain and liver concentrations of free hydrogen sulfide that are three orders of magnitude less than conventionally accepted values and only 1/5,000 of the hydrogen sulfide concentration (100 μM) required to alter cellular function in vitro. For hydrogen sulfide to serve as an endogenously produced messenger, tissue production and catabolism must result in intracellular microenvironments with a sufficiently high hydrogen sulfide concentration to activate a local signaling mechanism, while whole tissue concentrations remain very low.
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Tài liệu tham khảo
Blackstone E, Morrison M, Roth MB. H2S induces a suspended animation-like state in mice. Science 308: 518, 2002.
Cooper CE, Guilivi C. Nitric oxide regulation of mitochondrial oxygen consumption II: molecular mechanism and tissue physiology. Am J Physiol Cell Physiol 292: C2003–C2007, 2007.
Cotton FA, Wilkinson G. Advanced Inorganic Chemistry (5th ed.), New York: Wiley, 1988, p. 1455.
Dello Russo C, Tringali G, Ragazzoni E, Maggiano N, Menini E, Vairano M, Preziosi P, Navarra P. Evidence that hydrogen sulfide can modulate hypothalamo-pituitary-adrenal axis function: in vitro and in vivo studies in the rat. J Neuroendocrinol 12: 225–233, 2000.
Pedersen OO, Karlsen RL. The toxic effect of l-cysteine on the rat retina. A morphological and biochemical study. Invest Opthamol Vis Sci 19: 886–892, 1980.
Sax NI. Dangerous Properties of Industrial Materials. New York: Van Nostrand Reinhold, 1984, p. 1251.
Simonsen U, Wadsworth RW, Buus NH, Mulvany MJ. In vitro simultaneous measurements of relaxation and nitric oxide concentration in rat superior mesenteric artery. J Physiol 316: 271–282, 1999.
Tang G, Wu L, Liang W, Wang R. Direct stimulation of KATP channels by exogenous and endogenous hydrogen sulfide in vascular smooth muscle cells. Mol Pharmacol 68: 1757–1764, 2005.
Zhao W, Zhang J, Lu Y, Wang R. The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener. EMBRO J 20: 6008–6016, 2001.