Regulation of Hydrogen Sulfide Production in Blood Vessels.
Location
Bobo Room, Hodgin Hall, Third Floor
Start Date
8-11-2017 2:15 PM
End Date
8-11-2017 3:15 PM
Abstract
Hydrogen sulfide (H2S) is a colorless gas with a distinct odor of rotten eggs that is produced by many cells in the body. At high concentrations, H2S is toxic; however, at low concentrations, H2S has many positive effects including protecting cells from oxidative damage and regulating blood pressure. Cells produce H2S via several enzymes. In blood vessels, cystathionine gamma-lyase enzyme (CSE) makes most of the H2S. Once produced in blood vessels, H2S causes blood vessels to dilate or open up to increase blood flow into organs and tissues. Recent studies have found a dramatic loss of both H2S and CSE in many diseases including Type 2 Diabetes, Alzheimer’s disease, certain types of cancers and high blood pressure. Even though we have learned much about H2S chemistry, the regulation of H2S production by CSE is not known. Some studies suggest increases in calcium (Ca2+) activates the CSE enzyme. However, follow-up studies have not confirmed this observation and there is no consensus on the role Ca2+ plays in regulating CSE. The goal of this study was to identify regulators of CSE production of H2S in blood vessels. Endothelial cells from rat blood vessels were grown in culture dishes and treated with a chemical that fluoresces when it is exposed to H2S. Cells were then stimulated with either acetylcholine (ACh, 10 M), a blood vessel dilator; ionomycin (ion, 100 nM), a molecule that increases Ca2+ entry into cells; or sodium hydrosulfide (NaHS, 10 M), an H2S donor. Cells were treated for 30 minutes with either a CSE inhibitor (beta-cyanoalanine, BCA, 100 M) or a vehicle and changes in fluorescence were recorded. The blood vessel dilator ACh increased H2S production and this was blocked by the inhibitor of CSE. Increasing Ca2+ also activated CSE production of H2S. Our findings discovered that ACh-induced increases in intracellular Ca2+ increases CSE production of H2S. Future studies will investigate the targets of Ca2+ that interact with CSE to further delineate regulation of CSE activity.
Regulation of Hydrogen Sulfide Production in Blood Vessels.
Bobo Room, Hodgin Hall, Third Floor
Hydrogen sulfide (H2S) is a colorless gas with a distinct odor of rotten eggs that is produced by many cells in the body. At high concentrations, H2S is toxic; however, at low concentrations, H2S has many positive effects including protecting cells from oxidative damage and regulating blood pressure. Cells produce H2S via several enzymes. In blood vessels, cystathionine gamma-lyase enzyme (CSE) makes most of the H2S. Once produced in blood vessels, H2S causes blood vessels to dilate or open up to increase blood flow into organs and tissues. Recent studies have found a dramatic loss of both H2S and CSE in many diseases including Type 2 Diabetes, Alzheimer’s disease, certain types of cancers and high blood pressure. Even though we have learned much about H2S chemistry, the regulation of H2S production by CSE is not known. Some studies suggest increases in calcium (Ca2+) activates the CSE enzyme. However, follow-up studies have not confirmed this observation and there is no consensus on the role Ca2+ plays in regulating CSE. The goal of this study was to identify regulators of CSE production of H2S in blood vessels. Endothelial cells from rat blood vessels were grown in culture dishes and treated with a chemical that fluoresces when it is exposed to H2S. Cells were then stimulated with either acetylcholine (ACh, 10 M), a blood vessel dilator; ionomycin (ion, 100 nM), a molecule that increases Ca2+ entry into cells; or sodium hydrosulfide (NaHS, 10 M), an H2S donor. Cells were treated for 30 minutes with either a CSE inhibitor (beta-cyanoalanine, BCA, 100 M) or a vehicle and changes in fluorescence were recorded. The blood vessel dilator ACh increased H2S production and this was blocked by the inhibitor of CSE. Increasing Ca2+ also activated CSE production of H2S. Our findings discovered that ACh-induced increases in intracellular Ca2+ increases CSE production of H2S. Future studies will investigate the targets of Ca2+ that interact with CSE to further delineate regulation of CSE activity.
