Angiotensin II induces apoptosis in renal proximal tubular cells
Angiotensin II induces apoptosis in renal proximal tubular cells
复制标题
DOI：
10.1152/ajprenal.00246.2002
复制
发表时间：
2003-05-01
影响因子：
4.2
通讯作者：
Singhal, PC
中科院分区：
文献类型：
--
作者：
Bhaskaran, M;Reddy, K;Singhal, PC
ANG II已被证明在小管间质损伤的进展中发挥作用。我们研究了ANG II对培养大鼠肾近端小管上皮细胞凋亡的直接影响。ANG II以剂量和时间依赖的方式促进RPTEC细胞凋亡。抗转化生长因子(TGF)- β抗体可减弱ANG II的这种作用。此外，tgf - β以剂量依赖的方式触发RPTEC细胞凋亡。ANG II也增强了Fas和Fas配体（FasL）的RPTEC表达；此外，抗FasL抗体可减弱ANG II诱导的RPTEC细胞凋亡。此外，ANG II增加了细胞死亡蛋白Bax的RPTEC表达。ANG II型1 （AT(1)）和2型（AT(2)）受体阻滞剂均可抑制ANG II诱导的RPTEC细胞凋亡。p38 MAPK磷酸化抑制剂SB- 202190和caspase- 3抑制剂也能减弱ANG II诱导的RPTEC细胞凋亡。ANG II增强了RPTEC血红素加氧酶(HO)- 1的表达。有趣的是，hemin和姜黄素（HO- 1的诱导剂）预处理可以抑制ANG II诱导的小管细胞凋亡；相反，HO- 1表达抑制剂原卟啉锌预处理可促进ANG II的作用。这些结果表明，ANG II诱导的细胞凋亡是通过AT(1)和AT(2)受体介导的，通过TGF- β的产生，随后转录细胞死亡基因如Fas、FasL和Bax。调控HO- 1表达与ANGⅱ诱导的小管细胞凋亡呈反比关系。
ANG II has been demonstrated to play a role in the progression of tubulointerstial injury. We studied the direct effect of ANG II on apoptosis of cultured rat renal proximal tubular epithelial cells ( RPTECs). ANG II promoted RPTEC apoptosis in a dose- and time- dependent manner. This effect of ANG II was attenuated by anti- transforming growth factor ( TGF)-beta antibody. Moreover, TGF-beta triggered RPTEC apoptosis in a dose- dependent manner. ANG II also enhanced RPTEC expression of Fas and Fas ligand ( FasL); furthermore, anti- FasL antibody attenuated ANG II- induced RPTEC apoptosis. In addition, ANG II increased RPTEC expression of Bax, a cell death protein. Both ANG II type 1 ( AT(1)) and type 2 ( AT(2)) receptor blockers inhibited ANG II- induced RPTEC apoptosis. SB- 202190, an inhibitor of p38 MAPK phosphorylation, and caspase- 3 inhibitor also attenuated ANG II- induced RPTEC apoptosis. ANG II enhanced RPTEC heme oxygenase ( HO)- 1 expression. Interestingly, pretreatment with hemin as well as curcumin ( inducers of HO- 1) inhibited the ANG II- induced tubular cell apoptosis; conversely, pretreatment with zinc protoporphyrin, an inhibitor of HO- 1 expression, promoted the effect of ANG II. These results suggest that ANG II- induced apoptosis is mediated via both AT(1) and AT(2) receptors through the generation of TGF- beta, followed by the transcription of cell death genes such as Fas, FasL, and Bax. Modulation of tubular cell expression of HO- 1 has an inverse relationship with the ANG II- induced tubular cell apoptosis.