|Title:||Nickel(II) induced JNK activation-regulated mitochondria-dependent apoptotic pathway leading to cultured rat pancreatic β-cell death||Authors:||Wu H.-C.
|Issue Date:||2011||Journal Volume:||289||Start page/Pages:||103-111||Source:||Toxicology||Abstract:||
Nickel (Ni), a well-known toxic metal, is widely used in electroplating and alloy production. It is also significantly implicated in industrial and environmental pollution caused by uncontrolled industrial and municipal discharges. In this study, we characterized and investigated the cytotoxic effects of Ni exposure and their probable toxicological mechanisms in the pancreatic β-cells. The results showed that it was significantly decreased cell viability after exposing pancreatic β-cell-derived RIN-m5F cells to NiCl2 for 24h in a dose-dependent manner. NiCl2 also increased sub-G1 hypodiploid cells and Annexin V-Cy3 binding population in RIN-m5F cells, indicating that it has apoptosis-inducing ability. Moreover, the exposure of RIN-m5F cells to NiCl2 induced distinct signals of mitochondria-dependent apoptosis, including mitochondrial dysfunction (the disruption of mitochondrial membrane potential (MMP) and increase in mitochondrial cytochrome c release into the cytosol), Bak and Bid mRNA up-regulation, and activation of caspase-3, caspase-7, and caspase-9, and poly(ADP-ribose) polymerase (PARP) degradation. In addition, NiCl2 also markedly induced the activation of c-Jun N-terminal kinases (JNK), but not of extracellular signal-regulated kinase (ERK)1/2 and p38. These NiCl2-induced apoptosis-related signaling responses could be effectively reversed by specific JNK inhibitor SP600125. To the best of our knowledge, this study is the first to show that Ni causes pancreatic β-cell death through a JNK activation-regulated mitochondria-dependent apoptosis-signaling pathway. © 2011.
|ISSN:||0300-483X||DOI:||10.1016/j.tox.2011.07.013||SDG/Keyword:||anthra[1,9 cd]pyrazol 6(2h) one; beta actin; caspase 3; caspase 7; caspase 9; cytochrome c; DNA; lipocortin 5; messenger RNA; mitogen activated protein kinase; mitogen activated protein kinase 11; nickel chloride; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; protein Bak; protein Bid; animal cell; apoptosis; article; cell viability; controlled study; cytotoxicity; enzyme activation; LD 50; mitochondrial membrane potential; mitochondrion; nonhuman; pancreas islet beta cell; priority journal; protein binding; protein expression; rat; upregulation; Animals; Apoptosis; Cell Death; Cell Survival; Cells, Cultured; Enzyme Activation; Enzyme Induction; Insulin-Secreting Cells; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System; Membrane Potential, Mitochondrial; Mitochondria; Nickel; Rats; Rattus
|Appears in Collections:||醫學系|
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