Induction of VMAT-1 and TPH-1 expression induces vesicular accumulation of serotonin and protects cells and tissue from cooling/rewarming injury.

Abstract

DDT₁ MF-2 hamster ductus deferens cells are resistant to hypothermia due to serotonin secretion from secretory vesicles and subsequent cystathionine beta synthase (CBS) mediated formation of H₂S. We investigated whether the mechanism promoting resistance to hypothermia may be translationally induced in cells vulnerable to cold storage. Thus, VMAT-1 (vesicular monoamino transferase) and TPH-1 (tryptophan hydroxylase) were co-transfected in rat aortic smooth muscle cells (SMAC) and kidney tissue to create a serotonin-vesicular phenotype (named VTSMAC and VTkidney, respectively). Effects on hypothermic damage were assessed. VTSMAC showed a vesicular phenotype and an 8-fold increase in serotonin content and 5-fold increase in its release upon cooling. Cooled VTSMAC produced up to 10 fold higher concentrations of H₂S, and were protected from hypothermia, as shown by a 50% reduction of caspase 3/7 activity and 4 times higher survival compared to SMAC. Hypothermic resistance was abolished by the inhibition of CBS activity or blockade of serotonin re-uptake. In VTkidney slices, expression of CBS was 3 fold increased in cold preserved kidney tissue, with two-fold increase in H₂S concentration. While cooling induced substantial damage to empty vector transfected kidney as shown by caspase 3/7 activity and loss of FABP1, VTkidney was fully protected and comparable to non-cooled control. Thus, transfection of VMAT-1 and TPH-1 induced vesicular storage of serotonin which is triggered release upon cooling and has protective effects against hypothermia. The vesicular serotonergic phenotype protects against hypothermic damage through re-uptake of serotonin inducing CBS mediated H₂S production both in cells and kidney slices.

• Authors: Fatemeh Talaei, Martina Schmidt, Robert H Henning
• Journal: PloS one (PLoS One) Vol. 7 Issue 1 Pg. e30400 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22253933 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Slc18a1 protein, rat
• Vesicular Monoamine Transport Proteins
• Serotonin
• Collagen
• Tryptophan Hydroxylase
• tph1 protein, rat
• Hydrogen Sulfide

Topics

• Animals
• Aorta (pathology)
• Collagen (metabolism)
• Cricetinae
• Cytoprotection
• Enzyme Induction
• Hydrogen Sulfide (metabolism)
• Hypothermia (pathology, prevention & control)
• Kidney (metabolism, pathology)
• Male
• Myocytes, Smooth Muscle (enzymology, pathology)
• Phenotype
• Rats
• Rats, Sprague-Dawley
• Rewarming
• Secretory Vesicles (metabolism)
• Serotonin (metabolism)
• Transfection
• Tryptophan Hydroxylase (biosynthesis)
• Vesicular Monoamine Transport Proteins (metabolism)