Estrogenic Alkylphenols Induce Cell Death by Inhibiting Testis Endoplasmic Reticulum Ca2+ Pumps

作者: P.J. Hughes , H. McLellan , D.A. Lowes , S.Zafar Kahn , J.G. Bilmen

DOI: 10.1006/BBRC.2000.3710

关键词:

摘要: Industrial alkylphenols in the environment may act as “xenoestrogens” to disrupt testicular development and decrease male fertility. Amongst possible targets for these compounds are Sertoli cells, which nurture developing sperm cells. We demonstrate that SERCA 2 3 Ca2+ pumps relatively abundant rat testis microsomal membranes, also Sertoli, myoid, TM4 cells (a cell line). A number of estrogenic such nonylphenol, octylphenol, bisphenol A, butylated hydroxytoluene all inhibit ATPase low micromolar concentration range. These agents mobilize intracellular intact a manner consistent with inhibition ER pumps. Alkylphenols dramatically viability an effect is reversed by either caspase inhibitor or BAPTA, therefore Ca2+-dependent death via apoptosis. postulate inhibiting pumps, thus disturbing homeostasis.

参考文章(32)
J Lytton, M Westlin, S.E. Burk, G.E. Shull, D.H. MacLennan, Functional comparisons between isoforms of the sarcoplasmic or endoplasmic reticulum family of calcium pumps. Journal of Biological Chemistry. ,vol. 267, pp. 14483- 14489 ,(1992) , 10.1016/S0021-9258(19)49738-X
F Martinez-Azorin, J.A. Teruel, F Fernandez-Belda, J.C. Gomez-Fernandez, Effect of diethylstilbestrol and related compounds on the Ca(2+)-transporting ATPase of sarcoplasmic reticulum. Journal of Biological Chemistry. ,vol. 267, pp. 11923- 11929 ,(1992) , 10.1016/S0021-9258(19)49785-8
F Michelangeli, F Di Virgilio, A Villa, P Podini, J Meldolesi, T Pozzan, Identification, kinetic properties and intracellular localization of the (Ca2+-Mg2+)-ATPase from the intracellular stores of chicken cerebellum Biochemical Journal. ,vol. 275, pp. 555- 561 ,(1991) , 10.1042/BJ2750555
Stephen C. Tovey, Rita E. Godfrey, Phillip J. Hughes, Mokdad Mezna, Stephen D. Minchin, Katsuhiko Mikoshiba, Francesco Michelangeli, IDENTIFICATION AND CHARACTERIZATION OF INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS IN RAT TESTIS Cell Calcium. ,vol. 21, pp. 311- 319 ,(1997) , 10.1016/S0143-4160(97)90119-6
Samir S. Raychoudhury, Charles A. Blake, Clarke F. Millette, Toxic effects of octylphenol on cultured rat spermatogenic cells and Sertoli cells. Toxicology and Applied Pharmacology. ,vol. 157, pp. 192- 202 ,(1999) , 10.1006/TAAP.1999.8664
Graham R. Brown, Sarah L. Benyon, Christopher J. Kirk, Matthew Wictome, J.Malcolm East, Anthony G. Lee, Francesco Michelangeli, Characterisation of a novel Ca2+ pump inhibitor (bis-phenol) and its effects on intracellular Ca2+ mobilization. Biochimica et Biophysica Acta. ,vol. 1195, pp. 252- 258 ,(1994) , 10.1016/0005-2736(94)90264-X
Simon A. Rudge, Phillip J. Hughes, Graham R. Brown, Robert H. Michell, Christopher J. Kirk, Inositol lipid-mediated signalling in response to endothelin and ATP in the mammalian testis Molecular and Cellular Biochemistry. ,vol. 149, pp. 161- 174 ,(1995) , 10.1007/978-1-4615-2015-3_17
Robert M. Harris, Rosemary H. Waring, Christopher J. Kirk, Philip J. Hughes, Sulfation of “Estrogenic” Alkylphenols and 17β-Estradiol by Human Platelet Phenol Sulfotransferases Journal of Biological Chemistry. ,vol. 275, pp. 159- 166 ,(2000) , 10.1074/JBC.275.1.159
Sten Orrenius, David J. McConkey, Giorgio Bellomo, Pierluigi Nicotera, Role of Ca2+ in toxic cell killing Trends in Pharmacological Sciences. ,vol. 10, pp. 281- 285 ,(1989) , 10.1016/0165-6147(89)90029-1
Terri Meehan, Stefan Schlatt, Moira K. O'Bryan, David M. de Kretser, Kate Lakoski Loveland, Regulation of germ cell and Sertoli cell development by activin, follistatin, and FSH. Developmental Biology. ,vol. 220, pp. 225- 237 ,(2000) , 10.1006/DBIO.2000.9625