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Kaohsiung, Taiwan

Kuo C.-C.,Tzu Hui Institute of Technology | Huang J.-K.,Kaohsiung Veterans General Hospital | Chou C.-T.,Chang Gung Institute of Technology | Cheng J.-S.,Yongkang Veterans Hospital | And 8 more authors.
Drug and Chemical Toxicology | Year: 2011

The effect of the environmental contaminant, bisphenol A, on cytosolic free Ca 2+ concentrations ([Ca 2+]i) in Madin-Darby canine kidney (MDCK) cells is unclear. This study explored whether bisphenol A changed basal [Ca 2+]i levels in suspended MDCK cells by using fura-2 as a Ca 2+-sensitive fluorescent dye. Bisphenol A, at concentrations between 50 and 300 M, increased [Ca 2+]i in a concentration-dependent manner. The Ca 2+ signal was reduced, partly, by removing extracellular Ca 2+. Bisphenol A induced Mn 2+ influx, leading to quenching of fura-2 fluorescence, suggesting Ca 2+ influx. This Ca 2+ influx was inhibited by phospholipase A2 inhibitor aristolochic acid, store-operated Ca 2+ channel blockers nifedipine and SK&F96365, and protein kinase C inhibitor GF109203X. In Ca 2+-free medium, pretreatment with the mitochondrial uncoupler, carbonylcyanide m-chlorophenylhydrazone (CCCP), and the endoplasmic reticulum Ca 2+ pump inhibitors, thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ), inhibited bisphenol Ainduced Ca 2+ release. Conversely, pretreatment with bisphenol A abolished thapsigargin (or BHQ)-and CCCP-induced [Ca 2+]i rise. Inhibition of phospholipase C with U73122 abolished bisphenol-induced [Ca 2+]i rise. Bisphenol A caused a concentration-dependent decrease in cell viability via apoptosis in a Ca 2+-independent manner. Collectively, in MDCK cells, bisphenol A induced [Ca 2+]i rises by causing phospholipase Cdependent Ca 2+ release from the endoplasmic reticulum and mitochondria and Ca 2+ influx via phospholipase A2, protein kinase Csensitive, store-operated Ca 2+ channels. © 2011 Informa Healthcare USA, Inc. Source

Kuo C.-C.,Tzu Hui Institute of Technology | Kuo C.-C.,National Sun Yat - sen University | Kuo D.-H.,Tajen University | Huang C.-J.,Kaohsiung Medical University | And 6 more authors.
Drug Development Research | Year: 2010

Environmental chemicals may affect human health by disrupting endocrine function. Many endocrine disrupting chemicals (EDCs) are estrogen-like molecules that are classified as xenoestrogens (XEs). One XE, nonylphenol, is used as a surfactant or plasticizer and exhibits biotoxicity when accumulated in the body via the food chain. The aim of the present study was to clarify the role of nonylphenol-induced SCM1 apoptosis by measuring cultured human gastric cancer cell (SCM1) death. Using WST-1 reduction and propidium iodide-staining assays, nonylphenol treatment was found to activate caspase-3 and mitogen-activated protein kinases (MAPKs), major markers in apoptotic pathways. Nonylphenol also activated the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK). However, only SB203580 (a p38MAPK inhibitor) partially inhibited nonylphenol-induced apoptosis. Nonylphenol induced a [Ca 2+]i rise by causing extracellular Ca2+ influx and intracellular Ca2+ release from the endoplasmic reticulum, and its effects on SCM1 cell death were prevented by pretreatment with the Ca 2+ chelator BAPTA/AM. These results suggest that nonylphenol caused Ca2+-dependent apoptosis via the activation of p38 MAPK-associated caspase-3 in SCM1 cells. © 2009 Wiley-Liss, Inc. Source

Huang C.-H.,National Sun Yat - sen University | Chen Y.-J.,National Sun Yat - sen University | Chao T.-Y.,Laboratory Medicine Division | Liu W.-H.,National Sun Yat - sen University | And 4 more authors.
Journal of Cellular Physiology | Year: 2016

The primary cause of treatment failures in acute myeloid leukemia is usually associated with defects in the apoptotic pathway. Several studies suggest that 2-(4-aminophenyl)-7-methoxybenzothiazole (7-OMe-APBT) may potentially induce apoptosis of cancer cells. Thus, the present study was conducted to explore the cytotoxic effect of 7-OMe-APBT on human leukemia U937 cells. The apoptosis of human leukemia U937 cells induced by 7-OMe-APBT was characterized by an increase in mitochondrial membrane depolarization, procaspase-8 degradation, and tBid production. Down-regulation of FADD blocked 7-OMe-APBT-induced procaspase-8 degradation and rescued the viability of 7-OMe-APBT-treated cells, suggesting the involvement of a death receptor-mediated pathway in 7-OMe-APBT-induced cell death. Increased TNF-α expression, TNFR2 expression, and p38 MAPK phosphorylation were noted in 7-OMe-APBT-treated cells. Pretreatment with a p38 MAPK inhibitor abolished 7-OMe-APBT-induced TNF-α and TNFR2 up-regulation. 7-OMe-APBT stimulated p38 MAPK/c-Jun-mediated transcriptional up-regulation of TNFR2, while the increased TNF-α mRNA stability led to TNF-α up-regulation in 7-OMe-APBT-treated cells. Treatment with 7-OMe-APBT up-regulated protein phosphatase 2A catalytic subunit α (PP2Acα) expression via the p38 MAPK/c-Jun/ATF-2 pathway, which, in turn, promoted tristetraprolin (TTP) degradation. Pretreatment with a protein phosphatase 2A inhibitor or TTP over-expression abrogated TNF-α up-regulation in 7-OMe-APBT-treated cells. Abolishment of TNF-α up-regulation or knock-down of TNFR1/TNFR2 by siRNA restored the viability of 7-OMe-APBT-treated cells. Taken together, our data indicate a connection between p38 MAPK-mediated TNF-α and TNFR2 up-regulation and 7-OMe-APBT-induced TNF-α-mediated death pathway activation in U937 cells. The same pathway also elucidates the mechanism underlying 7-OMe-APBT-induced death of human leukemia HL-60 cells. © 2015 Wiley Periodicals, Inc. Source

Chen C.-C.,Kaohsiung Medical University | Yen H.-W.,Kaohsiung Medical University | Lo Y.-H.,Zuoying Armed Forces General Hospital | Chu Y.-H.,Laboratory Medicine Division | And 2 more authors.
Journal of Occupational and Environmental Medicine | Year: 2013

Objectives: The aim of this study was to examine the association of lead exposure with cardiac conduction disturbance among lead-exposed and nonexposed workers in Taiwan. Methods: The participants comprised 312 lead workers and 329 referents who had no known occupational lead exposure. During their annual health examination, they were invited to take part in the survey. Standard resting 12-lead electrocardiograms were obtained and the electrocardiographic features studied were related to blood lead levels (BLLs). Results: The mean BLLs were 26.05 (SD = 13.98) and 2.62 (SD = 1.42) μg/dL in lead-exposed and reference groups, respectively. Compared with the referents, lead workers had significantly shorter PR interval and longer QTc interval. Especially, workers with BLL > 30 μg/dL had the highest risk after adjusting for age, sex, body mass index, and other potential confounders. Conclusion: The data suggest that lead exposure is positively associated with prolonged QTc interval. Copyright © 2013 by American College of Occupational and Environmental Medicine. Source

Cheng J.-S.,Yongkang Veterans Hospital | Shu S.-S.,Kaohsiung Veterans General Hospital | Kuo C.-C.,Tzu Hui Institute of Technology | Chou C.-T.,Chang Gung Institute of Technology | And 9 more authors.
Archives of Toxicology | Year: 2011

The effect of diindolylmethane, a natural compound derived from indole-3-carbinol in cruciferous vegetables, on cytosolic Ca 2+ concentrations ([Ca 2+] i) and viability in HA59T human hepatoma cells is unclear. This study explored whether diindolylmethane changed [Ca 2+] i in HA59T cells. The Ca 2+-sensitive fluorescent dye fura-2 was applied to measure [Ca 2+] i. Diindolylmethane at concentrations of 1-50 μM evoked a [Ca 2+] i rise in a concentration-dependent manner. The signal was reduced by removing Ca 2+. Diindolylmethane-induced Ca 2+ influx was not inhibited by nifedipine, econazole, SK&F96365, and protein kinase C modulators but was inhibited by aristolochic acid. In Ca 2+-free medium, treatment with the endoplasmic reticulum Ca 2+ pump inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited or abolished diindolylmethane-induced [Ca 2+] i rise. Incubation with diindolylmethane inhibited thapsigargin or BHQ-induced [Ca 2+] i rise. Inhibition of phospholipase C with U73122 reduced diindolylmethane-induced [Ca 2+] i rise. At concentrations of 10-75 μM, diindolylmethane killed cells in a concentration-dependent manner. The cytotoxic effect of diindolylmethane was not reversed by chelating cytosolic Ca 2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N′, N′-tetraacetic acid. Propidium iodide staining data suggest that diindolylmethane (25-50 μM) induced apoptosis in a concentration-dependent manner. Collectively, in HA59T cells, diindolylmethane induced a [Ca 2+] i rise by causing phospholipase C-dependent Ca 2+ release from the endoplasmic reticulum and Ca 2+ influx via phospholipase A 2-sensitive channels. Diindolylmethane induced cell death that may involve apoptosis. © 2011 Springer-Verlag. Source

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