Bull Natalie D, Wood John P, Osborne Neville N, Barnett Nigel L
Vision, Touch and Hearing Research Centre, School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia.
Curr Eye Res. 2007 Feb;32(2):123-31. doi: 10.1080/02713680601139200.
It has previously been shown that inhibitors of protein kinase C (PKC) attenuate retinal glutamate uptake in situ. The aim of the current study was to determine whether PKCdelta-mediated inhibition differentially reduces the transport of glutamate into retinal Müller cells when compared with retinal neurons. The influence of two different types of PKC inhibitors on the uptake of [3H]D-aspartate was therefore compared in the intact retina, mixed retinal cultures, and Müller cell-enriched retinal cultures. It was found that 25 microM of the pan-isoform PKC inhibitor, chelerythrine, reduced [3H]D-aspartate uptake by 78%, 71%, and 68% in isolated retinas, mixed neuronal/glial cultures, and Müller cell-enriched cultures, respectively. Importantly, 20 microM of the PKCdelta-selective inhibitor rottlerin also reduced the uptake of D-aspartate to similar extents in all three systems, and the reductions were statistically similar to those found for the pan-specific PKC inhibitor. Neither pan-isoform nor PKCdelta-selective activators stimulated glutamate uptake in either culture system or the intact retina. The current results suggest that specific PKC inhibitors are quantitatively similar in reducing the uptake of glutamate into retinal neurons and Müller cells.
先前的研究表明，蛋白激酶C（PKC）抑制剂可减弱视网膜原位谷氨酸的摄取。本研究的目的是确定与视网膜神经元相比，PKCδ介导的抑制作用是否会不同程度地减少谷氨酸向视网膜穆勒细胞的转运。因此，在完整视网膜、混合视网膜培养物和富含穆勒细胞的视网膜培养物中比较了两种不同类型的PKC抑制剂对[3H]D-天冬氨酸摄取的影响。结果发现，25μM的泛亚型PKC抑制剂白屈菜红碱分别使分离的视网膜、混合神经元/神经胶质细胞培养物和富含穆勒细胞的培养物中[3H]D-天冬氨酸的摄取减少了78%、71%和68%。重要的是，20μM的PKCδ选择性抑制剂rottlerin在所有三个系统中也使D-天冬氨酸的摄取减少到相似程度，且减少程度与泛特异性PKC抑制剂的结果在统计学上相似。在任一培养系统或完整视网膜中，泛亚型或PKCδ选择性激活剂均未刺激谷氨酸的摄取。目前的结果表明，特定的PKC抑制剂在减少谷氨酸向视网膜神经元和穆勒细胞的摄取方面在数量上相似。
