Heme Oxygenase-1 Attenuates Glucose-Mediated Cell Growth Arrest and Apoptosis in Human Microvessel Endothelial Cells Export

@article{citeulike:5743474, abstract = {Heme oxygenase-1 (HO-1) is a stress protein that has been suggested to participate in defense mechanisms against agents that may induce oxidative injury, such as heme and inflammatory molecules. Incubation of endothelial cells in a high-glucose (33 mmol/L) medium for 7 days resulted in a decrease of HO activity by 34\% and a decrease in HO-1 and HO-2 proteins compared with cells exposed to low glucose (5 mmol/L) (P<0.05) or cells exposed to mannitol (33 mmol/L). Overexpression of HO-1 was coupled with an increase in HO activity and carbon monoxide synthesis, decreased cellular heme, and acceleration in all phases of the cell cycle (P<0.001). The rate of cell cycle or cell birth rate was increased by 29\% (P<0.05) in cells overexpressing HO-1 but decreased by 23\% (P<0.05) in cells underexpressing HO-1 compared with control cells. Exposure to high glucose significantly decreased cell-cycle progression in control cells and in cells underexpressing HO-1 but did not decrease cell-cycle progression in cells overexpressing HO-1. High glucose induced p21 and p27 in control cells but not in cells overexpressing HO-1. The addition of tin-mesoporphyrin (SnMP), an inhibitor of HO activity, reversed the HO-1-mediated decrease of p21 and p27 in cells overexpressing HO-1. These findings identify a novel effect of HO-1 on endothelial cell growth and indicate that heme metabolism and HO-1 expression regulate signaling systems in cells exposed to high glucose, which controls cell-cycle progression. 10.1161/01.RES.0000091828.36599.34}, author = {Abraham, Nader G. and Kushida, Taketoshi and McClung, Jack and Weiss, Melvin and Quan, Shuo and Lafaro, Rocky and Darzynkiewicz, Zbigniew and Wolin, Michael}, citeulike-article-id = {5743474}, citeulike-linkout-0 = {http://dx.doi.org/10.1161/01.RES.0000091828.36599.34}, citeulike-linkout-1 = {http://circres.ahajournals.org/cgi/content/abstract/93/6/507}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/12933701}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=12933701}, day = {19}, doi = {10.1161/01.RES.0000091828.36599.34}, journal = {Circ Res}, keywords = {adiponectin}, month = {September}, number = {6}, pages = {507--514}, posted-at = {2009-09-08 16:49:32}, priority = {3}, title = {Heme Oxygenase-1 Attenuates Glucose-Mediated Cell Growth Arrest and Apoptosis in Human Microvessel Endothelial Cells}, url = {http://dx.doi.org/10.1161/01.RES.0000091828.36599.34}, volume = {93}, year = {2003} }

TY - JOUR ID - citeulike:5743474 L3 - citeulike-article-id:5743474 N2 - Heme oxygenase-1 (HO-1) is a stress protein that has been suggested to participate in defense mechanisms against agents that may induce oxidative injury, such as heme and inflammatory molecules. Incubation of endothelial cells in a high-glucose (33 mmol/L) medium for 7 days resulted in a decrease of HO activity by 34% and a decrease in HO-1 and HO-2 proteins compared with cells exposed to low glucose (5 mmol/L) (P<0.05) or cells exposed to mannitol (33 mmol/L). Overexpression of HO-1 was coupled with an increase in HO activity and carbon monoxide synthesis, decreased cellular heme, and acceleration in all phases of the cell cycle (P<0.001). The rate of cell cycle or cell birth rate was increased by 29% (P<0.05) in cells overexpressing HO-1 but decreased by 23% (P<0.05) in cells underexpressing HO-1 compared with control cells. Exposure to high glucose significantly decreased cell-cycle progression in control cells and in cells underexpressing HO-1 but did not decrease cell-cycle progression in cells overexpressing HO-1. High glucose induced p21 and p27 in control cells but not in cells overexpressing HO-1. The addition of tin-mesoporphyrin (SnMP), an inhibitor of HO activity, reversed the HO-1-mediated decrease of p21 and p27 in cells overexpressing HO-1. These findings identify a novel effect of HO-1 on endothelial cell growth and indicate that heme metabolism and HO-1 expression regulate signaling systems in cells exposed to high glucose, which controls cell-cycle progression. 10.1161/01.RES.0000091828.36599.34 IS - 6 JF - Circ Res EP - 514 TI - Heme Oxygenase-1 Attenuates Glucose-Mediated Cell Growth Arrest and Apoptosis in Human Microvessel Endothelial Cells VL - 93 SP - 507 KW - adiponectin AU - Abraham, Nader AU - Kushida, Taketoshi AU - McClung, Jack AU - Weiss, Melvin AU - Quan, Shuo AU - Lafaro, Rocky AU - Darzynkiewicz, Zbigniew AU - Wolin, Michael PY - 2003/09/19/ UR - http://dx.doi.org/10.1161/01.RES.0000091828.36599.34 ER -