Serotonin and dopamine protect from hypothermia/rewarming damage through the CBS/H2S pathway

Fatemeh Talaei*, Hjalmar Bouma, Adrianus Van der Graaf, Arjen Strijkstra, Martina Schmidt, Robert Henning

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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-beta-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 5'-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 3 degrees C followed by 30 min of rewarming at 37 degrees C upregulated the expression of CBS, strongly reduced caspase activity and maintained the physiological pH compared to untreated tissues. Thus, dopamine and serotonin protect cells against hypothermia/rewarming induced damage by increasing H2S production mediated through CBS. Our data identify a novel molecular link between biogenic amines and the H2S pathway, which may profoundly affect our understanding of the biological effects of monoamine neurotransmitters.

Original languageEnglish
Article number22568
Number of pages11
JournalPLoS ONE
Volume6
Issue number7
DOIs
Publication statusPublished - 27-Jul-2011

Keywords

  • CYSTATHIONINE-BETA-SYNTHASE
  • RAT VAS-DEFERENS
  • HYDROGEN-SULFIDE
  • ISCHEMIA-REPERFUSION
  • REDOX REGULATION
  • MICE
  • H2S
  • INJURY
  • INHIBITION
  • KIDNEY

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