title: Cadmium-induced apoptosis in human normal liver L-02 cells by acting on mitochondria and regulating Ca(2+) signals.
abstract: Cadmium is a well-known toxic compound for the liver. It has been demonstrated to induce hepatotoxicity partly via apoptosis, but no uniform mechanism of apoptosis has so far been proposed. This study was first to determine whether cadmium-induced apoptosis in L-02 cells, second to observe the mechanism of cadmium-induced apoptosis. Studies of morphology, DNA fragmentation and apoptotic rate demonstrated that 60μM cadmium induced apoptosis with strong effects on cell viability. A concomitant time-dependent decrease of Bcl-2 and mitochondrial transmembrane potential (ΔΨ(m)) was observed. Subsequently, increase of caspase-3 activity and release of mitochondrial AIF were detected. However, cell pretreatment with a broad-specificity caspase inhibitor (Z-Asp) did not abolish apoptosis. These data demonstrated that the apoptotic events involved a mitochondria-mediated apoptotic pathway but not necessarily caspase-dependent signaling. On the other hand, intracellular free Ca(2+) concentration ([Ca(2+)](i)) of cadmium-exposed cells had significant increases and the Bapta-AM, a well-known calcium chelator, pretreatment partially blocked cadmium-induced apoptosis, indicating that the elevation of [Ca(2+)](i) may play an important role in the apoptosis. Together, these results support the notion that cadmium-induced hepatotoxicity is comparable to effects in L-02 by inducing apoptotic pathways on the basis of acting on mitochondria and regulating Ca(2+) signals.
authors.affiliation: College of Life Sciences, Nanjing Normal University, 122 Ninghai Road, Nanjing 210097, Jiangsu Province, People's Republic of China; Medical Science Department, Yangzhou Vocational College of Environment and Resources, 33 Runyangnan Road, Yangzhou 225127, Jiangsu Province, People's Republic of China.
authors.forename: Ji-Lin
authors.initials: JL
authors.lastname: Ye
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Mao
authors.forename: Ai-Lian
authors.initials: AL
authors.lastname: Wu
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Zhang
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: You-Jiang
authors.initials: YJ
authors.lastname: Yu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Chuan-Jing
authors.initials: CJ
authors.lastname: Wei