biostudies-literaturePresley TNIBIB NIH HHSNHLBI NIH HHSNIGMS NIH HHS38194-203https://www.ebi.ac.uk/biostudies/studies/S-EPMC2992253biostudies-literatureUnknown285(49)Uncoupling of NO production from NADPH oxidation by endothelial nitric-oxide synthase (eNOS) is enhanced in hyperglycemic endothelium, potentially due to dissociation of heat shock proteins 90 (Hsp90), and cellular glucose homeostasis is enhanced by a ROS-induced positive feed back mechanism. In this study we investigated how such an uncoupling impacts oxygen metabolism and how the oxidative phosphorylation can be preserved by heat shock (42 °C for 2 h, hyperthermia) in bovine aortic endothelial cells. Normal and heat-shocked bovine aortic endothelial cells were exposed to normoglycemia (NG, 5.0 mM) or hyperglycemia (30 mM). With hyperglycemia treatment, O(2) consumption rate was reduced (from V(O(2)max) = 7.51 ± 0.54 to 2.35 ± 0.27 mm Hg/min/10(6) cells), whereas in heat-shocked cells, O(2) consumption rate remained unaltered (8.19 ± 1.01 mm Hg/min/10 × 10(6) cells). Heat shock was found to enhance Hsp90/endothelial NOS interactions and produce higher NO. Moreover, ROS generation in the hyperglycemic condition was also reduced in heat-shocked cells. Interestingly, glucose uptake was reduced in heat-shocked cells as a result of decrease in Glut-1 protein level. Glucose phosphate dehydrogenase activity that gives rise to NADPH generation was increased by hyperthermia, and mitochondrial oxidative metabolism was preserved. In conclusion, the present study provides a novel mechanism wherein the reduced oxidative stress in heat-shocked hyperglycemic cells down-regulates Glut-1 and glucose uptake, and fine-tuning of this pathway may be a potential approach to use for therapeutic benefit of diabetes mellitus.The Journal of biological chemistryHyperthermia-induced Hsp90·eNOS preserves mitochondrial respiration in hyperglycemic endothelial cells by down-regulating Glut-1 and up-regulating G6PD activity.PMC2992253R21 EB004658R01 HL078796F31 GM078772-01F31 GM078772Presley TIlangovan GVedam KDruhan LJfalseHyperthermia-induced Hsp90·eNOS preserves mitochondrial respiration in hyperglycemic endothelial cells by down-regulating Glut-1 and up-regulating G6PD activity.Uncoupling of NO production from NADPH oxidation by endothelial nitric-oxide synthase (eNOS) is enhanced in hyperglycemic endothelium, potentially due to dissociation of heat shock proteins 90 (Hsp90), and cellular glucose homeostasis is enhanced by a ROS-induced positive feed back mechanism. In this study we investigated how such an uncoupling impacts oxygen metabolism and how the oxidative phosphorylation can be preserved by heat shock (42 °C for 2 h, hyperthermia) in bovine aortic endothelial cells. Normal and heat-shocked bovine aortic endothelial cells were exposed to normoglycemia (NG, 5.0 mM) or hyperglycemia (30 mM). With hyperglycemia treatment, O(2) consumption rate was reduced (from V(O(2)max) = 7.51 ± 0.54 to 2.35 ± 0.27 mm Hg/min/10(6) cells), whereas in heat-shocked cells, O(2) consumption rate remained unaltered (8.19 ± 1.01 mm Hg/min/10 × 10(6) cells). Heat shock was found to enhance Hsp90/endothelial NOS interactions and produce higher NO. Moreover, ROS generation in the hyperglycemic condition was also reduced in heat-shocked cells. Interestingly, glucose uptake was reduced in heat-shocked cells as a result of decrease in Glut-1 protein level. Glucose phosphate dehydrogenase activity that gives rise to NADPH generation was increased by hyperthermia, and mitochondrial oxidative metabolism was preserved. In conclusion, the present study provides a novel mechanism wherein the reduced oxidative stress in heat-shocked hyperglycemic cells down-regulates Glut-1 and glucose uptake, and fine-tuning of this pathway may be a potential approach to use for therapeutic benefit of diabetes mellitus.2010-01-01T00:00:00Z2010 Dec2021-02-20T21:43:58Z2019-03-27T00:36:55ZS-EPMC29922532086102010.1074/jbc.M110.14772810.1074/jbc.m110.147728