title: Cell apoptosis induced by zinc deficiency in osteoblastic MC3T3-E1 cells via a mitochondrial-mediated pathway.
abstract: Deficiency of zinc plays an important role in the pathogenesis of osteoporosis; however, the underlying mechanism is not well understood. Apoptosis of osteoblast causing the loss of bone mass is an important event in the osteoporosis. In this article, we investigated whether zinc deficiency would induce cell apoptosis in MC3T3-E1 cells and ask if it is involved in mitochondrial-mediated pathway. Significant increased apoptosis were observed in zinc deficiency group (ZnD: 5 μM TPEN and 1 μM zinc) compared with untreated control or zinc adequacy group (ZnA: 5 μM TPEN and 15 μM zinc). The mitochondrial membrane potential was strikingly reduced in ZnD group. Furthermore, we observed that the levels of Bax in mitochondria fraction and cyto c, AIF, and cleaved caspase-3/-9 in cytosol fraction were increased in ZnD group. We proposed that zinc deficiency would induce the translocation of Bax into mitochondria, which could lead to the reduction in mitochondrial membrane potential as well as the increase in mitochondrial membrane permeability. In addition, cyto c and AIF were released from mitochondria into the cytosol, which finally activated caspase-dependent and caspase-independent apoptosis processes in MC3T3-E1 cells. Our findings suggested that zinc deficiency is capable of inducing apoptosis through a mitochondria-mediated pathway in osteoblastic cells.
authors: Department of Orthopedics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
authors: Baolei
authors: B
authors: Guo
authors: Maowei
authors: M
authors: Yang
authors: Dan
authors: D
authors: Liang
authors: Lei
authors: L
authors: Yang
authors: Junjun
authors: J
authors: Cao
authors: Le
authors: L
authors: Zhang
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport; D015032:Zinc / Q000172:deficiency*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D061945:Caspase Inhibitors; D009842:Oligopeptides; D051028:bcl-2-Associated X Protein; C517629:benzyloxycarbonyl-valyl-alanyl-aspartic acid; D045304:Cytochromes c; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9; D015032:Zinc