Significance of Alteration of Phospholipase C-δ1 in the Brain Tissues through Oxidative Stress

当高氧诱导大鼠大脑皮层氧化应激时，大鼠大脑皮层中磷脂酶C (PLC)-β1和-δ1蛋白水平显著升高，而PLC-γ1蛋白水平无明显变化。上述结果表明，高氧对大鼠大脑皮层产生氧化应激，改变了PLC-β1和-δ1蛋白水平，但未改变PLC-γ1蛋白水平。丙烯腈（CAN）似乎通过选择性地诱导大鼠脑氧化应激诱导星形细胞瘤。用CAN治疗大鼠，但不加高氧，可导致心脏和大脑皮层脂质过氧化，且对后者的影响大于前者。在经can处理的大脑皮层中，胞浆中PLC-β1和-δ1，胞浆和颗粒组分以及裂解物中PLC-γ1均显著升高。在无法检测到PLC-β1的大鼠心脏中，高氧作用使PLC-γ1和-δ1在胞浆和颗粒组分中分别升高和降低。此外，裂解液中PLC-γ - 1的表达水平降低。在CAN处理的心脏中，PLC-γ - 1水平没有变化，而PLC-δ1在各部位均升高。我们已经证明，在作为外周组织的心脏和作为中心组织的大脑皮层中，高氧诱导的氧化应激明显小于CAN给药诱导的氧化应激。在两种氧化应激下，PLC同工酶的蛋白水平都发生了改变，但不同氧化应激水平和器官之间的蛋白水平变化有明显差异。为了进一步了解PLC同工酶对中枢神经系统发育和衰老的作用，采用免疫化学方法检测大鼠脑caspase家族蛋白在发育和衰老过程中的表达及其亚细胞分布。

When oxidative stress is induced in the rat cerebral cortex through hyperoxia, the protein levels of phospholipase C (PLC)-β1 and -δ1 were significantly increased in the cerebral cortex, although that of PLC-γ1 was not altered. These results suggest that hyperoxia exerts oxidative stress on the rat cerebral cortex, and the protein levels of PLC-β1 and -δ1, but not PLC-γ1, were changed. Acrylonitrile (CAN) appears to induce astrocytomas through induction of oxidative stress on the rat brain selectively. Treatment of rats with CAN, but not hyperoxia, resulted in lipid peroxidation in the heart and cerebral cortex, and the effect on the latter was greater than on the former. In the CAN-treated cerebral cortex, significant increases in the PLC-β1 and -δ1 in the cytosol, and PLC-γ1 in the cytosolic and particulate fractions, and lysate were observed. In the rat heart, in which PLC-β1 could not be detected, PLC-γ1 and -δ1 were increased and decreased in the cytosolic and particulate fractions, respectively, by hyperoxia. In addition, the expression level of PLC-γ1 was decreased in the lysate by the treatment. In the heart treated with CAN, there was no change in the level of PLC-γ1, while PLC-δ1 was elevated in all fractions. We have demonstrated that oxidative stress induced by hyperoxia is apparently less than that induced by CAN administration in the heart as a peripheral tissue and the cerebral cortex as a central one. With both forms of oxidative stress, the protein levels of PLC isozymes were altered, but there was apparent difference in the altered protein levels between the different levels of oxidative stress, and between the organs. In order to obtain the information about contribution of PLC isozymes to the central nervous system development and aging, the expression of rat brain caspase family proteins in development and aging, and their subcellular distribution were also assessed using immunochemical detection.