Nitric oxide and bcl-2 mediated the apoptosis induced by nickel(II) in human T hybridoma cells.
Although effects of nickel(II) on the immune system have long been recognized, little is known about the effects of nickel(II) on the induction of apoptosis and related signaling events in T cells. In the present study, we investigated the roles and signaling pathways of nickel(II) in the induction of apoptosis in a human T cell line jurkat. The results showed that the cytotoxic effects of Ni involved significant morphological changes and chromosomal condensation (Hoechst 33258 staining). Analyses of hypodiploid cells and FITC-Annexin V and PI double staining showed significant increase of apoptosis in jurkat cells 6, 12 and 24 h after nickel(II) treatment. Flow cytometry analysis also revealed that the loss of mitochondrial membrane potential (MMP) occurred concomitantly with the onset of NiCl(2)-induced apoptosis. Induction of apoptotic cell death by nickel was mediated by reduction of bcl-2 expression. Furthermore, nickel stimulated the generation of nitric oxide (NO). These results suggest that nickel(II) chloride induces jurkat cells apoptosis via nitric oxide generation, mitochondrial depolarization and bcl-2 suppression.
Guan
Fuqin
F
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, PR China.
Zhang
Dongmei
D
Wang
Xinchang
X
Chen
Junhui
J
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006825:Hybridomas; D019169:Jurkat Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009532:Nickel / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D051025:bcl-Associated Death Protein / Q000235:genetics*
D017304:Annexin A5; D001562:Benzimidazoles; D012333:RNA, Messenger; D051025:bcl-Associated Death Protein; C447680:hoechst 32258; D009569:Nitric Oxide; C022838:nickel chloride; D009532:Nickel