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

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 H(2)S production by the endogenous enzyme cystathionine-?-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 H(2)S 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 H(2)S 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°C followed by 30 min of rewarming at 37°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 H(2)S production mediated through CBS. Our data identify a novel molecular link between biogenic amines and the H(2)S pathway, which may profoundly affect our understanding of the biological effects of monoamine neurotransmitters.

SUBMITTER: Talaei F

PROVIDER: S-EPMC3144905 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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

Talaei Fatemeh F Bouma Hjalmar R HR Van der Graaf Adrianus C AC Strijkstra Arjen M AM Schmidt Martina M Henning Robert H RH

PloS one 20110727 7

Biogenic amines have been demonstrated to protect cells from apoptotic cell death. Herein we show for the first time that serotonin and dopamine increase H(2)S production by the endogenous enzyme cystathionine-β-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 H(2)S production in cultured rat smooth muscle cel ...[more]

PMID: 21829469

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Project description:Hypothermia and acidosis are secondary causes of trauma-related coagulopathy. Here we report the case of a 72-year-old patient with severe trauma who suffered near-severe hypothermia despite the initiation of standard warming measures and was successfully managed with active intravascular rewarming. The patient was involved in a road traffic accident and was transported to a hospital. He was diagnosed with massive right-sided hemothorax, blunt aortic injury, burst fractures of the eighth and ninth thoracic vertebrae, and open fracture of the right tibia. He was referred to our hospital, where emergency surgery was performed to control bleeding from the right hemothorax. During surgery, the patient demonstrated progressive heat loss despite standard rewarming measures, and his temperature decreased to 32.4°C. Severe acidosis was also observed. A Cool Line® catheter was inserted into the right femoral vein and lodged in the inferior vena cava, and an intravascular balloon catheter system was utilized for aggressive rewarming. The automated target core temperature was set at 37°C, and the maximum flow rate was used. His core temperature reached 36.0°C after 125 min of intravascular rewarming. The severe acidosis was also resolved. The main active bleeding site was not identified, and coagulation hemostasis as well as rewarming enabled us to control bleeding from the vertebral bodies, lung parenchyma, and pleura. The total volume of intraoperative bleeding was 5,150 mL, and 20 units of red cell concentrate and 16 units of fresh frozen plasma were transfused. After surgery, he was transferred to the intensive care unit under endotracheal intubation and mechanical ventilation. His hemodynamic condition stabilized after surgery. The rewarming catheter was removed on day 2 of admission, and no bleeding, infection, or thrombosis associated with catheter placement was observed. Extubation was performed on day 40, and his subsequent clinical course was uneventful. He recovered well following rehabilitation and was discharged on day 46. These findings suggest that active intravascular rewarming should be considered as an aggressive, additional rewarming technique in patients with near-severe hypothermia associated with traumatic injury.

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

Publications

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

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