Lin H |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=4.469 ------>paper_class3=2 ------>paper_class2=1 ------>vol=72 ------>confirm_bywho=ncchang ------>insert_bywho=sueym ------>Jurnal_Rank=13.1 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=1245 ------>medlineContent= ------>unit=E0109 ------>insert_date=20080313 ------>iam=7 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN=0026-895X ------>authors_c= ------>score=500 ------>journal_name=Molecular pharmacology ------>paper_name=Peroxisomal proliferator-activated receptor-alpha protects renal tubular cells from doxorubicin-induced apoptosis. ------>confirm_date=20080320 ------>tch_id=093141 ------>pmid=17671096 ------>page1=1238 ------>fullAbstract=Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a transcription factor and has been reported to inhibit cisplatin-mediated proximal tubule cell death. In addition, doxorubicin (Adriamycin)-induced nephrosis in rats is a commonly used experimental model for pharmacological studies of human chronic renal diseases. In this study, we investigated the protective effect of PPAR-alpha on doxorubicin-induced apoptosis and its detailed mechanism in NRK-52E cells and animal models. The mRNA level of PPAR-alpha was found to be reduced by doxorubicin treatment in NRK-52E cells. PPAR-alpha overexpression in NRK-52E cells significantly inhibited doxorubicin-induced apoptosis and the quantity of cleaved caspase-3. Endogenous prostacyclin (PGI(2)) augmentation, which has been reported to protect NRK-52E cells from doxorubicin-induced apoptosis, induced the translocation and activation of PPAR-alpha. The transformation of PPAR-alpha short interfering RNA was applied to silence the PPAR-alpha gene, which abolished the protective effect of PGI(2) augmentation in doxorubicin-treated cells. To confirm the protective role of PPAR-alpha in vivo, PPAR-alpha activator docosahexaenoic acid (DHA) was administered to doxorubicin-treated mice, and it has been shown to significantly reduce the doxorubicin-induced apoptotic cells in renal cortex. However, this protective effect of DHA did not exist in PPAR-alpha-deficient mice. In NRK-52E cells, the overexpression of PPAR-alpha elevated the activity of catalase and superoxide dismutase and inhibited doxorubicin-induced reactive oxygen species (ROS). PPAR-alpha overexpression also inhibited the doxorubicin-induced activity of nuclear factor-kappaB (NF-kappaB), which was associated with the interaction between PPAR-alpha and NF-kappaB p65 subunit as revealed in immunoprecipitation assays. Therefore, PPAR-alpha is capable of inhibiting doxorubicin-induced ROS and NF-kappaB activity and protecting NRK-52E cells from doxorubicin-induced apoptosis. ------>tmu_sno=None ------>sno=16749 ------>authors2=Hou CC ------>authors3=Cheng CF ------>authors4=Chiu TH ------>authors5=Hsu YH ------>authors6=Sue YM,Chen TH,Hou HH,Chao YC,Cheng TH,Chen CH. ------>authors6_c= ------>authors=Lin H ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Peroxisomal proliferator-activated receptor-alpha protects renal tubular cells from doxorubicin-induced apoptosis. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=5 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2007 ------>submit_flag=None ------>publish_month=11 |