The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

High glucose level inhibits capacitative Ca2+ influx in cultured rat mesangial cells by a protein kinase C-dependent mechanism.

In cultured mesangial cells (MC), capacitative Ca2+ influx via store-operated channels (SOC) is potentiated by agents that release Ca2+ from intracellular stores, and inhibited by protein kinase C ( PKC). Cells grown under high glucose conditions, as a model of the diabetic microenvironment, display reduced Ca2+ signalling in response to vasoconstrictors, probably due to downregulation by elevated PKC activity. Since SOC might be relevant to this phenomenon, we assessed Ca2+ influx by microfluorometry of fura-2-loaded rat MC cultured for 5 days in normal (5.5 mmol/l, NG) or high glucose (30 mmol/l, HG). The addition of 1-10 mmol/l Ca2+ to NG cells equilibrated in Ca(2+)-free media induced an immediate Ca2+ influx with a free cytosolic Ca2+ ([Ca2+]i) plateau of 155 +/- 50 and 318 +/- 114 nmol/l, respectively. Basal influx was reduced to 88 +/- 8 and 145 +/- 17 nmol/l [Ca2+]i (1-10 mmol/l Ca2+, p < 0.01) by 30 mmol/l D-glucose. This effect of HG was confirmed by Mn2+ quenching of fura-2, indicating reduced entry of divalent cations via the capacitative pathway. Equimolar L-glucose had no effect on Ca2+ influx, consistent with a non-osmotic mechanism. Arginine vasopressin (10 mumol/l) elicited weaker release of stored Ca2+ and subsequent influx in HG cells (191 +/- 33 vs 153 +/- 24 nmol/l, 400 +/- 76 vs 260 +/- 33 nmol/l, 1-10 mmol/l Ca2+, NG/HG, p < 0.05). To examine the involvement of PKC in the effect of HG on capacitative Ca2+ influx, the enzyme was activated or downregulated by treatment with 0.1 mumol/l phorbol myristate acetate (PMA) for 3 min or 24 h, respectively. PMA acutely inhibited Ca2+ influx in NG cells, while PKC downregulation restored it in HG cells. Similarly, the PKC inhibitors staurosporin or H-7 normalized SOC activity in HG cells. In summary, impairment of Ca2+ influx via SOC by HG is one mechanism of the reduced MC [Ca2+]i responsiveness to vasoconstrictors. This event is mediated by PKC and may contribute to the glomerular haemodynamic changes in the initial stages of diabetes mellitus.[1]

References

  1. High glucose level inhibits capacitative Ca2+ influx in cultured rat mesangial cells by a protein kinase C-dependent mechanism. Menè, P., Pugliese, G., Pricci, F., Di Mario, U., Cinotti, G.A., Pugliese, F. Diabetologia (1997) [Pubmed]
 
WikiGenes - Universities