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.
Bishara
N B
NB
School of Medical Sciences, Royal Melbourne Institute of Technology University, Bundoora, Victoria, Australia.
Ding
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H
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