| Shih CM, Ko WC, Wu JS, Wei YH, Wang LF, Chang EE, Lo TY ,Cheng HH, Chen CT |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=2.946 ------>paper_class3=2 ------>paper_class2=1 ------>vol=91 ------>confirm_bywho=cmshih ------>insert_bywho=cmshih ------>Jurnal_Rank=38.7 ------>authors4_c= ------>comm_author=1 ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=397 ------>medlineContent= ------>unit=E0103 ------>insert_date=20031015 ------>iam=1 ------>update_date= ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c= ------>score=500 ------>journal_name=J. Cell. Biochem. ------>paper_name=Mediating of caspase-independent apoptosis by cadmium through the mitochondria-ROS pathway in MRC-5 fibroblasts ------>confirm_date=20060505 ------>tch_id=085008 ------>pmid=14743397 ------>page1=384 ------>fullAbstract=Cadmium (Cd) is an environmental pollutant of global concern with a 10-30-year biological half-life in humans. Accumulating evidence suggests that the lung is one of the major target organs of inhaled Cd compounds. Our previous report demonstrated that 100 microM Cd induces MRC-5 cells, normal human lung fibroblasts, to undergo caspase-independent apoptosis mediated by mitochondrial membrane depolarization and translocation of apoptosis-inducing factor (AIF) from mitochondria into the nucleus. Here, using benzyloxycarbonyl-Val-Ala-Asp-(ome) fluoromethyl ketone (Z-VAD.fmk) as a tool, we further demonstrated that Cd could induce caspase-independent apoptosis at concentrations varied from 25 to 150 microM, which was modulated by reactive oxygen species (ROS) scavengers, such as N-acetylcysteine (NAC), mannitol, and tiron, indicating that ROS play a crucial role in the apoptogenic activity of Cd. Consistent with this notion, the intracellular hydrogen peroxide (H2O2) was 2.9-fold elevated after 3 h of Cd treatment and diminished rapidly within 1 h as detected by flow cytometry with 2~,7~-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Using inhibitors of the mitochondrial electron transport chain (ETC) (oligomycin A and rotenone for complex I and V, respectively) and mitochondrial permeability transition pore (MPTP) (cyclosporin A and aristolochic acid), we coincidently found the ROS production, mitochondrial membrane depolarization, and apoptotic content were almost completely or partially abolished. As revealed by confocal microscopy staining with chloromethyl-X-rosamine (CMXRos) and an anti-AIF antibody, the collapse of mitochondrial membrane potential induced by Cd (3 h-treatment) was a prelude to the translocation of caspase-independent pro-apoptotic factor, AIF, into the nucleus (after 4 h of Cd treatment). In summary, this study demonstrated that, in MRC-5 fibroblasts, Cd induced caspase-independent apoptosis through a mitochondria-ROS pathway. More importantly, we provide several lines of evidence supporting a role of mitochondrial ETC and MPTP in the regulation of caspase-independent cell death triggered by Cd. ------>tmu_sno=None ------>sno=7679 ------>authors2= ------>authors3= ------>authors4= ------>authors5= ------>authors6= ------>authors6_c= ------>authors=Shih CM, Ko WC, Wu JS, Wei YH, Wang LF, Chang EE, Lo TY ,Cheng HH, Chen CT ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Mediating of caspase-independent apoptosis by cadmium through the mitochondria-ROS pathway in MRC-5 fibroblasts. ------>language=2 ------>check_flag= ------>submit_date= ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho= ------>publish_year=2004 ------>submit_flag= ------>publish_month=1 |