CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress.
CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress.
复制标题
DOI：
10.1371/journal.pone.0127507
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Du XG
中科院分区：
文献类型：
--
作者：
Hua W;Huang HZ;Tan LT;Wan JM;Gui HB;Zhao L;Ruan XZ;Chen XM;Du XG
由脂肪酸转位酶CD36介导的高脂血症诱导的细胞凋亡与巨噬细胞、肝细胞和近端肾小管上皮细胞摄取氧化低密度脂蛋白或脂肪酸的增加有关，从而导致动脉粥样硬化、肥胖患者的肝损伤和纤维化以及糖尿病肾病(DN)。然而，CD36在糖尿病肾病合并高脂血症患者足细胞凋亡中的具体作用尚不清楚。石蜡包埋肾组织(CTR=18，DN=20)采用免疫组织化学和免疫荧光染色方法检测CD36的表达。培养条件永生化的小鼠足细胞(MPC5)和用棕榈酸处理的细胞，用实时定量聚合酶链式反应、免疫印迹和免疫荧光检测CD36的表达，用油红O染色和BODIPY染色检测脂质摄取，用流式细胞仪、TUNEL法和Western印迹分析检测细胞凋亡，用DCFH-DA荧光染色检测细胞内ROS的产生。采用SPSS21.0统计软件进行统计分析。糖尿病肾病伴高脂血症患者肾组织CD36表达增加。棕榈酸可上调足细胞CD36的表达，并促进其从胞浆向质膜的转位。此外，棕榈酸增加了足细胞的脂质摄取、ROS产生和细胞凋亡，CD36上脂肪酸结合位点的特异性抑制剂磺基N-琥珀酰亚胺油酸(SSO)减少了棕榈酸诱导的脂肪酸积聚、ROS产生和足细胞凋亡。抗氧化剂4-羟基-2，2，6，6-四甲基哌啶-1-氧基(Tempoll)可抑制棕榈酸诱导的足细胞ROS过量产生和细胞凋亡。CD36介导的脂肪酸通过氧化应激诱导足细胞凋亡可能参与了糖尿病肾病的发病过程。
Hyperlipidemia-induced apoptosis mediated by fatty acid translocase CD36 is associated with increased uptake of ox-LDL or fatty acid in macrophages, hepatocytes and proximal tubular epithelial cells, leading to atherosclerosis, liver damage and fibrosis in obese patients, and diabetic nephropathy (DN), respectively. However, the specific role of CD36 in podocyte apoptosis in DN with hyperlipidemia remains poorly investigated. The expression of CD36 was measured in paraffin-embedded kidney tissue samples (Ctr = 18, DN = 20) by immunohistochemistry and immunofluorescence staining. We cultured conditionally immortalized mouse podocytes (MPC5) and treated cells with palmitic acid, and measured CD36 expression by real-time PCR, Western blot analysis and immunofluorescence; lipid uptake by Oil red O staining and BODIPY staining; apoptosis by flow cytometry assay, TUNEL assay and Western blot analysis; and ROS production by DCFH-DA fluorescence staining. All statistical analyses were performed using SPSS 21.0 statistical software. CD36 expression was increased in kidney tissue from DN patients with hyperlipidemia. Palmitic acid upregulated CD36 expression and promoted its translocation from cytoplasm to plasma membrane in podocytes. Furthermore, palmitic acid increased lipid uptake, ROS production and apoptosis in podocytes, Sulfo-N-succinimidyloleate (SSO), the specific inhibitor of the fatty acid binding site on CD36, decreased palmitic acid-induced fatty acid accumulation, ROS production, and apoptosis in podocytes. Antioxidant 4-hydroxy-2,2,6,6- tetramethylpiperidine -1-oxyl (tempol) inhibited the overproduction of ROS and apoptosis in podocytes induced by palmitic acid. CD36 mediated fatty acid-induced podocyte apoptosis via oxidative stress might participate in the process of DN.
登录
查看更多内容
影响因子：
2.5
作者：
Kriz, W
通讯作者：
Kriz, W
影响因子：
11.1
作者：
STENVINKEL, P;ALVESTRAND, A;BERGSTROM, J
通讯作者：
BERGSTROM, J
DOI：
10.1186/1755-1536-7-12
发表时间：
2014
期刊：
Fibrogenesis & tissue repair
影响因子：
--
作者：
Srivastava SP;Shi S;Koya D;Kanasaki K
通讯作者：
Kanasaki K
影响因子：
29
作者：
Seimon TA;Nadolski MJ;Liao X;Magallon J;Nguyen M;Feric NT;Koschinsky ML;Harkewicz R;Witztum JL;Tsimikas S;Golenbock D;Moore KJ;Tabas I
通讯作者：
Tabas I
影响因子：
4.2
作者：
KEESFOLTS, D;DIAMOND, JR
通讯作者：
DIAMOND, JR