| Huang WJ |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=0.540 ------>paper_class3=2 ------>paper_class2=1 ------>vol=29 ------>confirm_bywho=hsu0320 ------>insert_bywho=wjhuang ------>Jurnal_Rank=86.3 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=921 ------>medlineContent= ------>unit=G0200 ------>insert_date=20080505 ------>iam=1 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c= ------>score=500 ------>journal_name=Renal Failure ------>paper_name=Ras activation modulates methylglyoxal-induced mesangial cell apoptosis through superoxide production ------>confirm_date=20080508 ------>tch_id=096017 ------>pmid=17994461 ------>page1=911 ------>fullAbstract=AIMS: While previous studies have demonstrated that diabetic nephropathy is attributable to glucose-derived dicarbonyl compounds, methylglyoxal (MGO)-inducing apoptosis in renal mesangial cells, the molecular mechanism of upper stream redox signaling modulation, has not been fully elucidated. METHODS: Rat mesangial cells pretreated with or without superoxide dismutase, diphenyloniodium, SB203580, and manumycin A were cultured in methylglyoxal stress-induced apoptosis. Signaling protein expression, flow cytometry, and morphological features of apoptotic cell death were assessed. RESULTS: Methylglyoxal decreased cell viability in mesangial cells. Superoxide mediated methylglyoxal-induced caspase 3 cleavage. Pretreatment with diphenyloniodium, SB203580, and manumycin A reduced methylglyoxal augmentation of superoxide synthesis and caspase-3 activation. Methylglyoxal rapidly enhanced Ras activation and progressively increased cytosolic P38 and nuclear c-Jun activation. Scavenging of superoxide by superoxide dismutase or diphenyloniodium, inhibiting P38 by SB203580, and inhibiting Ras with manumycin A successfully reduced the promoting effect of methylglyoxal on P38 and c-Jun phosphorylation (activation). Furthermore, pretreatment with superoxide dismutase, diphenyloniodium, SB203580, and manumycin A significantly attenuated methylglyoxal induction of apoptosis on the basis of Annexin-V assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labelling (TUNEL) staining. CONCLUSIONS: This study has shown that methylglyoxal increased Ras modulation of superoxide-mediated P38 activation and c-Jun activation, which resulted in increased apoptosis. ------>tmu_sno=None ------>sno=18374 ------>authors2=Tung CW ------>authors3=Ho C ------>authors4=Yang JT ------>authors5=Huang CF ------>authors6=Chang PJ, Hsu YC, Lee PH, Lin CL ------>authors6_c= ------>authors=Huang WJ ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Ras activation modulates methylglyoxal-induced mesangial cell apoptosis through superoxide production. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2007 ------>submit_flag=None ------>publish_month=1 |