Glucose enhances expression of TRPC1 and calcium entry in endothelial cells

Abstract

Hyperglycemia is a major risk factor for endothelial dysfunction and vascular disease, and in the current study, the link to glucose-induced abnormal intracellular Ca2+ (Cai2+) 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 Cai2+ or ATP-induced Cai2+ release; however, the amplitude of sustained Cai2+ 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 Ca2+ entry in bovine aortic endothelial cells. Although the link between HG-induced changes in TRPC1 expression, enhanced Ca2+ 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.

Update on vascular endothelial Ca2+signalling: A tale of ion channels, pumps and transporters

“…TRPC1 is engaged by a number of inflammatory agonists, such as ATP, thrombin, tumor necrosis factor (ΤΝF)-α, and angiotensin II (AngII), and by growth factors, such as VEGF and bFGF [5,12,148,[207][208][209] . TRPC1 may act as a SOC due to its ability to interact with InsP3Rs through several signaling cascades.…”

“…Finally, TRPC1 may be involved in endothelial tube formation both in vitro [224] and in vivo [225] . The expression of TRPC1 in vascular ECs may be increased by high glucose levels, with a consequent increase in the amplitude of agonistinduced Ca 2+ influx and a dramatic impact on endothelial function in diabetic patients [209] . TRPC1 not only acts as an SOC in vascular endothelium, but may also serve as an MSC by assembling with TRPV4 to mediate flow-induced Ca 2+ entry in vascular endothelium [226] .…”

Calcium mediates high glucose-induced HIF-1α and VEGF expression in cultured rat retinal Müller cells through CaMKII-CREB pathway

“…Hyperglycemia is a pathological hallmark of diabetic complications, such as diabetic retinopathy (DR), and hyperglycemia can also increase the intracellular free calcium concentration ([Ca 2+ ] i ) in various cell types [1][2][3][4] . An increase in [Ca 2+ ] i has been shown to play an important role in the pathogenesis of angiogenesis [5,6] , which is the most common cause of blindness in DR. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic factors produced by retinal ischemia [7] .…”

Store-operated calcium entry and diabetic complications

“…Similarly, in bovine aortic endothelial cells, Bishara and Ding showed that high glucose treatment at 25 mM for 24 and 72 h resulted in a sustained increase in SOCE following activation of the P 2 Y receptor by ATP. 113 They proposed that the TRPC1 protein contributed to the enhanced SOCE because TRPC1 protein expression was elevated after 72-h high glucose treatment, and antisense TRPC1 treatment attenuated the ATP-induced Ca 2þ response. However, it is not clear whether the TRPC1 protein functions as an SOC itself or as a regulator/modulator of SOC in that study.…”