Glucose enhances expression of TRPC1 and calcium entry in endothelial cells.
Hyperglycemia is a major risk factor for endothelial dysfunction and vascular disease, and in the current study, the link to glucose-induced abnormal intracellular Ca(2+) (Ca(i)(2+)) homeostasis was explored in bovine aortic endothelial cells in high glucose (HG; 25 mmol/l) versus low glucose (LG; 5.5 mmol/l; control). Transient receptor potential 1 (TRPC1) ion channel protein, but not TRPC3, TRPC4, or TRPC6 expression, was significantly increased in HG versus LG at 72 h. HG for 4, 24, and 72 h did not change basal Ca(i)(2+) or ATP-induced Ca(i)(2+) release; however, the amplitude of sustained Ca(i)(2+) was significantly increased at 24 and 72 h and reduced by low concentration of the putative, but nonspecific, TRPC blockers, gadolinium, SKF-96365, and 2-aminoethoxydiphenyl borate. Treatment with TRPC1 antisense significantly reduced TRPC1 protein expression and ATP-induced Ca(2+) entry in bovine aortic endothelial cells. Although the link between HG-induced changes in TRPC1 expression, enhanced Ca(2+) entry, and endothelial dysfunction require further study, the current data are suggestive that targeting these pathways may reduce the impact of HG on endothelial function.
School of Medical Sciences, Royal Melbourne Institute of Technology University, Bundoora, Victoria, Australia.
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Bishara
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Ding
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D016375:Antisense Elements (Genetics); D016718:Arachidonic Acid / Q000494:pharmacology; D015153:Blotting, Western; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005682:Gadolinium / Q000494:pharmacology; D005947:Glucose / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D007202:Indicators and Reagents; D050052:TRPC Cation Channels / Q000096:biosynthesis* / Q000235:genetics*
C538758:2-aminoethyl diphenylborinate; D016375:Antisense Elements (Genetics); D001896:Boron Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007093:Imidazoles; D007202:Indicators and Reagents; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D016718:Arachidonic Acid; D000255:Adenosine Triphosphate; D005682:Gadolinium; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D005947:Glucose; D002118:Calcium