@article{APS7847,
author = {Jun Li and Shu-zhi Zhao and Pei-pei Wang and Song-ping Yu and Zhi Zheng and Xun Xu},
title = {Calcium mediates high glucose-induced HIF-1α and VEGF expression in cultured rat retinal Müller cells through CaMKII-CREB pathway},
journal = {Acta Pharmacologica Sinica},
volume = {33},
number = {8},
year = {2016},
keywords = {},
abstract = {Aim: To investigate the effects of high glucose (HG) medium on expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in cultured rat retinal Müller cells and to determine the signaling pathways mediating the effects.
Methods: Primary cultures of retinal Müller cells were prepared from Sprague-Dawley rats, and incubated in a medium containg HG (30 mmol/L) in the presence of the membrane-permeable Ca2+ chelator BAPTA-AM (10 μmol/L) or the CaMKII inhibitor KN93 (10 μmol/L). The levels of CaMKII, p-CaMKII, CREB, p-CREB, HIF-1α, and VEGF proteins were measured with Western blotting, while HIF-1á and VEGF mRNA levels were determined using real-time RT-PCR.
Results: The stimulation of retinal Müller cell with HG for 24 h remarkably increased the expression levels of HIF-1α and VEGF. These responses were significantly inhibited in the presence of BAPTA-AM or KN93. Both BAPTA-AM and KN93 also significantly inhibited HG-induced phosphorylation of CaMKII and CREB in the cultured retinal Müller cells. Transfection of the cultured retinal Müller cells with antisense CREB oligonucleotide (300 nmol/L) was similarly effective in blocking the HG-induced increase of HIF-1α and VEGF.
Conclusion: HG-induced HIF-1α and VEGF expression in cultured rat retinal Müller cells depends on intracellular free Ca2+ and activation of CaMKII-CREB pathway. The activation of CaMKII-CREB pathway by HG may be a possible mechanism underlying the pathogenesis of diabetic retinopathy.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/7847}
}