serotonin and dopamine protect from hypothermiarewarming damage through the cbs h2s pathway5 -羟色胺和多巴胺通过cbs h2s通路保护从hypothermiarewarming伤害.pdfVIP

Serotonin and Dopamine Protect from Hypothermia/ Rewarming Damage through the CBS/ H2S Pathway 1 1 2 1,3 Fatemeh Talaei *, Hjalmar R. Bouma , Adrianus C. Van der Graaf , Arjen M. Strijkstra , Martina Schmidt4, Robert H. Henning1 1 Department of Clinical Pharmacology (FB20), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, 2 Angteq B.V., Turftorenstraat, Groningen, The Netherlands, 3 Department of Chronobiology, University of Groningen, Groningen, The Netherlands, 4 Department of Molecular Pharmacology, Faculty of Pharmacy, University of Groningen, Groningen, The Netherlands Abstract Biogenic amines have been demonstrated to protect cells from apoptotic cell death. Herein we show for the first time that serotonin and dopamine increase H2S production by the endogenous enzyme cystathionine-b-synthase (CBS) and protect cells against hypothermia/rewarming induced reactive oxygen species (ROS) formation and apoptosis. Treatment with both compounds doubled CBS expression through mammalian target of rapamycin (mTOR) and increased H2S production in cultured rat smooth muscle cells. In addition, serotonin and dopamine treatment significantly reduced ROS formation. The beneficial effect of both compounds was minimized by inhibition of their re-uptake and by pharmacological inhibition of CBS or its down-regulation by siRNA. Exogenous administration of H2S and activation of CBS by Prydoxal 59-phosphate also protected cells from hypothermic damage. Finally, serotonin and dopamine pretreatment of rat lung, kidney, liver and heart prior to 24 h of hypothermia at 3uC followed by 30 min of rewarming at 37uC upregulated the expression of CBS, strongly reduced caspase acti