THE STUDY OF C KINASE ACTIVATOR CAUSE FOR THE PATHOLOGICAL CHANGES.

蛋白激酶C （PKC）在受体介导的信号转导中起着至关重要的作用，影响多种细胞反应，如细胞增殖、分化和肿瘤促进。PKC是一种独特的酶，由受体介导的磷酸肌醇水解产生的1,2-二酰基甘油（DAG）激活。另一方面，活性氧如超氧化物、过氧化氢和羟基自由基已被认为在许多病理事件中发挥重要作用，如炎症、自身免疫性疾病、缺血再灌注损伤、动脉粥样硬化和心血管疾病以及癌变。这表明PKC的作用与活性氧诱导的功能障碍和细胞损伤之间存在密切的关系，然而，这种可能性尚未得到彻底的研究。在本研究中，我们观察到1-硬脂酰-2-亚油基甘油过氧化氢（SLG- ooh）和SLG氢氧化物（SLG- oh）在磷脂酰丝氨酸和钙离子存在下比未氧化的SLG更有效地刺激了大鼠脑PKC的活性。1,2-二油酰基甘油过氧化氢（LLG-OOH）、LLG-OH、1-棕榈酰-2-亚油基甘油过氧化氢（PLG-OOH）、PLG-OH、1-硬脂酰-2-花生四烯酰基甘油过氧化氢（SAG-OOH）、SAG-OH、1-棕榈酰-2-花生四烯酰基甘油过氧化氢（PAG-OOH）、PAG-OH对大鼠脑PKC组分具有相似的生物学效应。一般认为DAG是由磷脂酶C （PLC）水解质膜磷脂酰肌醇1,5-二磷酸，或由磷脂酶D水解PC，随后磷脂酸转化为DAG而产生的。然而，最近有许多报道表明，DAG可以直接由各种哺乳动物细胞中含有的PC膜被PC特异性PLC水解而产生。此外，有报道称PLC比水解氧化PC更有优势。因此，很有可能氧化的DAG （DAG- ooh）来自氧化损伤的哺乳动物细胞膜。然后，DAG-OOH可能作为氧化应激的生化信使，以接近phorbol 12-肉豆蔻酸酯的方式改变pkc依赖的信号转导系统。另一方面，大鼠脑PKC片段含有α、β、γ、δ、epusilon、zeta的PKC同工型。有趣的是，SLG-OOH分别特异性激活PKC α和δ亚型。这些结果表明，PKC α和δ可以通过不相关的受体偶联水解1,5-二磷酸磷脂酰肌醇的方式被氧化应激激活。少

Protein kinase C (PKC) plays a crucial role a receptor-mediated signal transduction affecting diverse range of cellular responses such as cell proliferation, differentiation, and tumor promotion. PKC is a unique enzyme which is activated by 1,2-diacylglycerol (DAG) produced form receptor-mediated hydrolysis of inositol phosphate. On the othe hand, active oxygen species such as superoxide, hydrogen peroxide, and hydroxy radical have been suggested to play important roles in many pathological events such as inflammation, autoimmune diseases, ischemia-reperfusion injury, atherosclerosis and cardiovascular diseases, and carcinogenesis. This suggests a close relationship between the action of PKC and active oxygen speciesinduced dysfunction and cellular damage, however, this possibility has not been throughly examined. In the present study, we observed that 1-stearoyl-2-linoleoylglycerol hydroperoxide (SLG-OOH) and SLG hydroxide (SLG-OH) stimulated the PKC activity isolated from rat brain m … More ore efficiently than that of unoxidized SLG in the presences of phosphatidylserine and calcium ion. 1,2-dilinoleoylglycerol hydroperoxide (LLG-OOH), LLG-OH,1-palmitoyl-2-linoleoylglycerol hydroperoxide (PLG-OOH), PLG-OH,1-stearoyl-2-arachidonoylglycerol hydroperoxide (SAG-OOH), SAG-OH,1-palmitoyl-2-arachidonoylglycerol hydroperoxide (PAG-OOH), PAG-OH have similar biological effects on rat brain PKC fraction. It is generally accepted that DAG is generated from the hydrolysis of plasma membrane phosphatidylinositol 1,5-bisphosphate by phospholipase C (PLC), or from the hydrolysis of PC by phospholipase D and subsequent conversion of phosphatidic acid to DAG.Recently, however, many reports have disclosed that DAG could be generated directly from the hydrolysis of membrane PC contained in various mammalian cells by PC-specific PLC.Futhermore, it has been reported that PLC has a preference to hydrolyzed oxidized PC.Hence, it is quite conceivable that oxidized DAG (DAG-OOH) is from oxidatively damaged mammalian cell membranes. Then, DAG-OOH may act as a biochemical messenger of oxidative stress to alter the PKC-dependent signal transduction system in manner approaching phorbol 12-myristate acetate. On the other hand, rat brain PKC fraction contains PKC isoforms of alpha, beta, gamma, delta, epusilon, zeta. Interestigly, SLG-OOH specifically activated PKC alpha and delta isoforms, respectively. These results suggested that PKC alpha and delta can be activated through oxidative stress in a manner unrelated receptor-coupled hydrolysis of phosphatidylinositol 1,5-bisphosphate by PLC. Less