Agonist-induced calcium and oxidative stress responses in endothelial cells

Wilkinson, Jenny A.; Jacob, Ron

doi:10.1042/bst0310960

Cited by 8 publications

(4 citation statements)

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“…Furthermore, Steinert et al (2002) and Mahdy et al (1998) demonstrated that human fetal venous EC and maternal human hand vein EC show a loss of the sustained phase in subjects with preeclampsia, a condition that is characterized by hypertension (Mahdy et al 1998, Steinert et al 2002. This data along with our previous data on UAEC led us to believe that the sustained phase of the [Ca 2C ] i response in NP-UAEC is relatively unresponsive, while P-UAEC mobilize Ca 2C more like calf pulmonary artery EC, bovine aortic EC, and rat aortic EC (Chu et al 2000, Bishara et al 2002, Wilkinson & Jacob 2003.…”

Section: Introductionmentioning

confidence: 71%

Pregnancy-enhanced store-operated Ca2+ channel function in uterine artery endothelial cells is associated with enhanced agonist-specific transient receptor potential channel 3-inositol 1,4,5-trisphosphate receptor 2 interaction

Gifford¹,

Feng²,

Bird³

2006

Journal of Endocrinology

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We have previously shown that endothelial cells (EC) derived from the uterine artery (UA) of both pregnant (P-UAEC) and nonpregnant (NP-UAEC) ewes show a biphasic intracellular free Ca 2C ([Ca 2C ] i ) response after ATP stimulation. In each case, the initial transient peak, caused by the release of Ca 2C from the intracellular Ca 2C stores, is mediated by purinergic receptor-Y2 and is very similar in both cell types. However, the sustained phase in particular, caused by the influx of extracellular Ca 2C, is heightened in the P-UAEC, and associates with an increased ability of the cells to demonstrate enhanced capacitative Ca 2C entry (CCE) via store-operated channels (SOCs). Herein we demonstrated that the difference in the sustained [Ca 2C ] i response is maintained for at least 30 min. When 2-aminoethoxydiphenyl borate (2APB) (an inhibitor of the inosital 1,4,5-trisphosphate receptor (IP3R) and possibly SOC) was used in conjunction with ATP, it was capable of completely inhibiting CCE. Since 2APB can inhibit SOC in some cell types and 2APB was capable of inhibiting CCE in the UAEC model, the role of SOC in CCE was first evaluated using the classical inhibitor La ] i response. Since canonical transient receptor potential channels (TRPCs) have recently been identified as putative SOCs in many cell types, including EC, the expression levels of several isoforms were evaluated in UAEC. Expression of TRPC3 and TRPC6 channels in particular was detected, but no significant difference in expression level was found between NP-and P-UAEC. Nonetheless, we were able to show that IP3R2 interacts with TRPC3 in UAEC, forming a protein complex, and that this interaction is considerably enhanced in an agonist sensitive manner by pregnancy. Thus, while IP3R and TRPC isoforms are not altered in their expression by pregnancy, enhanced functional interaction of TRPC3 with IP3R2 may underlie pregnancy-enhanced CCE in the UAEC model and so explain the prolonged [Ca 2C ] i sustained phase seen in response to ATP.

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Section: Introductionmentioning

confidence: 71%

Pregnancy-enhanced store-operated Ca2+ channel function in uterine artery endothelial cells is associated with enhanced agonist-specific transient receptor potential channel 3-inositol 1,4,5-trisphosphate receptor 2 interaction

Gifford¹,

Feng²,

Bird³

2006

Journal of Endocrinology

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“…Binding of EPO to its receptor causes a rise of intracellular calcium levels (30) and thereby inhibits NO production and eNOS protein expression in endothelial cells (7). Recently, it was reported that ATP-stimulated cytosolic calcium increase is followed by an increase in ROS formation in endothelial cells (31).…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin Increases Asymmetric Dimethylarginine in Endothelial Cells

Scalera¹,

Kielstein²,

Martens‐Lobenhoffer³

et al. 2005

Journal of the American Society of Nephrology

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Recombinant human erythropoietin therapy frequently causes hypertension in humans and animals with chronic renal failure. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase, and its accumulation has been associated with reducing NO bioavailability and increasing superoxide generation. Whether epoetin ␤ (EPO) or darbepoetin ␣ (NESP) can modify the levels of ADMA in endothelial cells was investigated. Endothelial cells from the third passage were incubated for 24 h in the presence of various concentrations of EPO or NESP (0, 0.1, 1, 10, 50, 100, and 200 U/ml). The levels of ADMA, allantoin, nitrate, and nitrite in conditioned media and the activity of dimethylarginine dimethylaminohydrolase (DDAH), the content of thiols and reactive oxygen species in endothelial cells, were determined. When endothelial cells were exposed to EPO or NESP, ADMA concentration in the cell culture medium increased significantly in a dose-dependent manner versus control. This effect was associated with a reduced activity of DDAH, the enzyme that degrades ADMA. Furthermore, EPO-or NESP-induced accumulation of ADMA was accompanied by a significant reduction of NO synthesis and an increase in oxidative stress. Both allantoin, a marker of oxygen free radical generation, and reactive oxygen species increased significantly after EPO or NESP treatment compared with control. The antioxidant pyrrolidine dithiocarbamate preserved DDAH activity and reduced ADMA accumulation in the same way as the co-incubation with anti-EPO neutralizing antibody. EPO and NESP posttranslationally impair DDAH activity via increased oxidative stress, causing ADMA as an important cardiovascular risk factor to accumulate and inhibit NO synthesis.

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“…Recently, it was reported that agonist-stimulated cytosolic calcium increase is followed by an increase in ROS formation in endothelial cells. 36 Because TRPC5 channels are calcium permeable, elevated agonist-stimulated calcium influx through upregulated TRPC5 channels in endothelial cells during EPO treatment may contribute to the ROS formation, which underlies pathogenesis of EPO-induced hypertension.…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin Increases Expression and Function of Transient Receptor Potential Canonical 5 Channels

Liu

Thilo

et al. 2011

Hypertension

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Abstract-Hypertension is a common complication in hemodialysis patients during erythropoietin (EPO) treatment. The underlying mechanisms of EPO-induced hypertension still remain to be determined. Key Words: transient receptor potential channel Ⅲ erythropoietin Ⅲ hypertension E levated arterial blood pressure is a common adverse effect of erythropoietin (EPO) administration in patients and animal models with chronic kidney disease. [1][2][3][4] Several observations indicate that EPO-induced hypertension is not only mediated by changes in erythrocyte mass but also by direct adverse effects of EPO. The underlying mechanisms of EPO-induced rise in blood pressure still remain to be determined. 4,5 Considerable evidence has been accumulated for impaired cellular calcium homeostasis in EPO-associated hypertension. EPO significantly increases cytosolic free calcium concentration and expands sarcoplasmic calcium stores in platelets from essential hypertensive or EPO-associated hypertension patients and cultured vascular smooth muscle cells from rats. 6 -8 Transient receptor potential canonical (TRPC) channels are calcium-permeable nonselective cation channels that had been identified in many cell types, including endothelial cells and peripheral blood cells. 9 We previously showed significantly increased expression of functional TRPC5 channel protein in patients with essential hypertension and in spontaneously hypertensive rats. 10 -12 In the present study, we hypothesized that EPO increases the expression and function of the TRPC5 gene, finally contributing to the pathogenesis of hypertension. To test this hypothesis, we examined the effects of EPO on TRPC5 channel expression and function in cultured human endothelial cells and peripheral blood cells. Experimental Procedures Cell CultureHuman umbilical vein endothelial cell-derived EA.hy926 cells (American Type Culture Collection) were maintained at 37°C and 5% CO 2 in DMEM containing 10% FCS, 100 U/mL of penicillin, and 100 g/mL of streptomycin (BIOCHROM AG, Berlin, Germany). After detachment with 0.25% trypsin, cells were seeded in plates as appropriate, that is, 6-well plates for RNA and protein isolation, 12-well plates for patch clamp experiments, and 96-well

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Agonist-induced calcium and oxidative stress responses in endothelial cells

Cited by 8 publications

References 1 publication

Pregnancy-enhanced store-operated Ca2+ channel function in uterine artery endothelial cells is associated with enhanced agonist-specific transient receptor potential channel 3-inositol 1,4,5-trisphosphate receptor 2 interaction

Pregnancy-enhanced store-operated Ca2+ channel function in uterine artery endothelial cells is associated with enhanced agonist-specific transient receptor potential channel 3-inositol 1,4,5-trisphosphate receptor 2 interaction

Erythropoietin Increases Asymmetric Dimethylarginine in Endothelial Cells

Erythropoietin Increases Expression and Function of Transient Receptor Potential Canonical 5 Channels

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