Inhibition of poly(ADP-ribose) polymerase inhibits ischemia/reperfusion induced neurodegeneration in retina via suppression of endoplasmic reticulum stress.
Inhibition of poly(ADP-ribose) polymerase inhibits ischemia/reperfusion induced neurodegeneration in retina via suppression of endoplasmic reticulum stress.
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DOI：
10.1016/j.bbrc.2012.05.109
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发表时间：
2012-06
影响因子：
3.1
通讯作者：
Chuanzhou Li;Lei-lei Wang;T. Kern;Ling Zheng
中科院分区：
文献类型：
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作者：
Chuanzhou Li;Lei-lei Wang;T. Kern;Ling Zheng
Poly(ADP-ribose) polymerase (PARP) inhibitors have neuroprotective effects after retinal ischemia and reperfusion (I/R) injury, but mechanisms of this action are not clear. A second generation PARP inhibitor, GPI 15427, was administrated to mice to investigate the possible mechanisms underlying its neuroprotective effects after retinal I/R injury. Ischemia was induced by increasing intraocular pressure to 80–90mm Hg for 60min followed by reperfusion, and mice were treated with GPI 15427 (40mg/kg−1day−1, orally) 2days before or 1day after injury. Histopathology caused by the retinal I/R injury was estimated by TUNEL assay and histological analyses. Relative gene expressions were evaluated by RT-PCR, Western blotting and immunohistological studies. GPI 15427 inhibited the retinal I/R-induced PARP activation and glial cell activation. GPI 15427 also significantly inhibited the I/R-induced neurodegeneration, as well as increase in TUNEL-positive cells. I/R-induced PERK-eIF2α-CHOP activation and Bip over-expression were inhibited by GPI 15427, while it did not suppress I/R-induced CHOP over-expression and degeneration of retinal capillaries. Our results suggest that GPI 15427 inhibited retinal I/R-induced neurodegeneration and glial cell activation, and this was associated with an effect of the drug to suppress PERK-eIF2α-CHOP activation and Bip over-expression. These results provide evidence that GPI 15427 inhibits retinal I/R injury at least in part via inhibition of endoplasmic reticulum stress.
