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• W2131498907 abstract "Cadmium is a well-known carcinogenic and immunotoxic metal commonly found in cigarette smoke and industrial effluent. An altered intracellular calcium ([Ca2+]i) level has been implicated in the pathophysiology of immune dysfunction. The present study was designed to determine the possible involvement of calcium (Ca2+) and mitogen-activated protein kinases (MAPKs) signaling pathways on cadmium-induced cell death in J774A.1 murine macrophage cells. Cadmium caused a low-amplitude [Ca2+]i elevation at 20 μM and rapid and high-amplitude [Ca2+]i elevation at 500 μM. Exposure to cadmium dose-dependently induced phosphorylation of c-Jun NH2-terminal kinase (JNK) and deactivated p38 MAPK. Use of the selective JNK inhibitor SP600125 suggested that activation of JNK is pro-apoptotic and pro-necrotic. Buffering of the calcium response with 1,2-bis-(2-aminophenoxy)-ethane-N,N,N′,N′-tetraacetic acid tetrakis (acetoxy-methyl) ester (BAPTA-AM) and ethylene glycol-bis-(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA) completely blocked cadmium-induced apoptotic response. The pretreatment of cells with BAPTA-AM and EGTA suppressed the cadmium-induced cell injury, including growth arrest, mitochondrial activity impairment, and necrosis, and it also recovered the cadmium-altered JNK and p38 MAPK activity. Chelating [Ca2+]i also reversed cadmium-induced hydrogen peroxide generation, suggesting that production of reactive oxygen species (ROS) is related to [Ca2+]i. The present study showed that cadmium induces a [Ca2+]i-ROS-JNK-caspase-3 signaling pathway leading to apoptosis. Furthermore, cadmium-induced [Ca2+]i regulates phosphorylation/dephosphorylation of JNK and p38, and it modulates signal transduction pathways to proliferation, mitochondrial activity, and necrosis." @default.
• W2131498907 created "2016-06-24" @default.
• W2131498907 creator A5001090733 @default.
• W2131498907 creator A5033665939 @default.
• W2131498907 date "2004-07-14" @default.
• W2131498907 modified "2023-10-18" @default.
• W2131498907 title "Calcium-Mediated Activation of c-Jun NH2-Terminal Kinase (JNK) and Apoptosis in Response to Cadmium in Murine Macrophages" @default.
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• W2131498907 doi "https://doi.org/10.1093/toxsci/kfh221" @default.
• W2131498907 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15254339" @default.
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