摘要
目的:探讨蛋白激酶C(PKC)对肿瘤坏死因子-α(TNF-α)引起的肾小球前小动脉平滑肌细胞(RASMC)内Ⅰ型三磷酸肌醇(IP_3)受体mRNA过度表达的影响。方法:通过对RASMC的分离、培养,应用核酸杂交技术分别检测在TNF-α和PKC抑制剂、TNF-α和PKA抑制剂及PKC激动剂作用下,RASMC内Ⅰ型IP_3受体mRNA的表达情况。结果:TNF-α促进RASMC内Ⅰ型IP_3受体mRNA表达增加;PKC抑制剂明显抑制TNF-α诱导的Ⅰ型IP_3受体mRNA过度表达的作用(14814.0±2029.9,11334.0±1104.9,P<0.05);PKC激动剂能增强RASMC内Ⅰ型IP_3受体mRNA表达(22554.5±2625.2,28128.0±3698.6,P<0.05);PKA抑制剂-H_(89)不影响TNF-α诱导Ⅰ型IP_3受体mRNA的表达。结论:TNF-α影响细胞内储备Ca^(2+)释放信息传递系统可能通过激活PKC作用于Ⅰ型IP_3受体基因,使Ⅰ型IP_3受体mRNA合成增加,导致Ⅰ型IP_3受体蛋白过度表达,参与促进RASMC内储备Ca^(2+)大量释放至胞质,引起肾小球前小动脉平滑肌收缩,使肾血流量减少,肾小球滤过率下降,导致肾功能异常。
AIM: To investigate the effects of protein kinase C (PKC) on type Ⅰ inositol 1, 4, 5-triphosphate receptor (IP_3 R) expression in rat glomerular afferent arterioles smooth muscle cells (RASMC) treated with TNF-α. METHODS: RASMC were isolated and cultured from rats, type Ⅰ IP_3 R mRNA in RASMC treated with TNF-α and PKC activator or TNF-α and PKC inhibitor or PKC activator or PKC inhibitor were detected by Northern blot. RESULTS: TNF-α enhanced the expression of type Ⅰ IP_3 R mRNA in RASMC; PKC inhibitor significantly inhibited the expression of type Ⅰ IP_3 R mRNA induced by TNF-α (14 814.0±2 029.9, 11 334.0±1 104.9, P<0.05). PKC activator significantly enhanced the expression of type Ⅰ IP_3 R mRNA in RASMC treated without TNF-α(22 554.5±2 625.2, 28 128.0±3 698.6, P<0.05). PKA inhibitor could not inhibit the expression of type Ⅰ IP_3 R mRNA induced by TNF-α. CONCLUSION: TNF-α plays a role in signal transduction in RASMC. TNF-α may act as the promoter of type Ⅰ IP_3 R mRNA in RASMC or activates PKC that results in the expression of type Ⅰ IP_3 R protein. PKC and IP_3 promote releasing of intracellular Ca^(2+) in RASMC, inducing RASMC constrict. The renal blood flow diminution is involved in the development of renal dysfunction.
出处
《世界华人消化杂志》
CAS
2003年第6期705-707,共3页
World Chinese Journal of Digestology
基金
国家自然科学基金
No.39870337
