Stimulation of intracellular Ca2+ elevation in neutrophils by thiol-oxidizing phenylarsine oxide |
| |
Authors: | Wang Jih-Pyang Tsai Jaw-Ji Chen Yu-San Hsu Mei-Feng |
| |
Affiliation: | Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC. w1994@vghtc.gov.tw |
| |
Abstract: | Phenylarsine oxide (PAO), a trivalent arsenical compound, stimulated [Ca2+]i elevation in rat neutrophils in a Ca2+-containing medium but caused no appreciable response in a Ca2+-free medium. PAO also induced external Mn2+ entry, which was inhibited by N-acetyl-L-cysteine (NAC), but failed to elicit any appreciable Ba2+ and Sr2+ entry. Pretreatment of neutrophils with thiol-reducing agents including dithiothreitol (DTT), NAC, 2,3-dimercapto-1-propanol (DMP), 2,3-dimercaptopropane-1-sulfonic acid (DMPS) and tris-(2-carboxyethyl)phosphine (TCEP), all greatly inhibited PAO-induced [Ca2+]i elevation. Addition of Ni2+ or La3+ followed by PAO stimulation also attenuated the Ca2+ signals in a concentration-dependent manner. PAO had no significant effect on the production of reactive oxygen intermediates (ROI) and nitric oxide (NO) nor did it decrease cellular low molecular weight thiols levels. PAO-induced [Ca2+]i elevation was significantly inhibited by 1-[6-[17beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122), the inhibitor of phospholipase C-coupled processes, genistein, a general tyrosine kinase inhibitor, phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, calyculin A, a cortical actin stabilizer, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY 294002), a phosphoinositide 3-kinase inhibitor, 1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole (SKF-96365), and cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL-12,330A), the blockers of receptor-gated and store-operated Ca2+ channels, whereas there was no appreciable effect exerted by aristolochic acid, a phospholipase A2 inhibitor, 7-nitroindazole and N-(3-aminomethyl)benzylacetamidine (1400W), the blockers of NO synthase, and by suspension in a Na+-deprived medium. In contrast, 2-aminoethoxydiphenyl borane (2-APB), the blocker of IP3 receptor and Ca2+ influx, enhanced the PAO-induced response. PAO had no effect on the plasma membrane Ca2+-ATPase (PMCA) activity in the pharmacological isolated neutrophil preparation and the neutrophil membrane fractions. These results indicate that PAO stimulates [Ca2+]i rise in rat neutrophils mainly through the oxidation of vicinal thiol groups on the cell surface membrane to activation of a non-store operated Ca2+ entry (non-SOCE) without affecting the activity of PMCA and the plasmalemmal Na+/Ca2+ exchanger. |
| |
Keywords: | 1400W, N-(3-aminomethyl)benzylacetamidine AA, arachidonic acid 2-APB, 2-aminoethoxydiphenyl borane CPA, cyclopiazonic acid DAF-2/DA, 4,5-diaminofluorescein diacetate DMP, 2,3-dimercapto-1-propanol DMPS, 2,3-dimercaptopropane-1-sulfonic acid DTT, dithiothreitol GEA3162, 5-amino-3-(3,4-dichlorophenyl)1,2,3,4-oxatriazolium HBSS, Hanks’ balanced salt solution H2DCF/DA, 2′,7′-dichlorodihydrofluorescein diacetate IP3, smallcaps" >d-myo-inositol 1,4,5-trisphosphate LY 294002, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one mBBr, monobromobimane MDL-12,330A, cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine NAC, N-acetyl- smallcaps" >l-cysteine NO, nitric oxide PAO, phenylarsine oxide PIK3, phosphoinositde-3-kinase PKC, protein kinase C PLC, phospholipase C PMA, phorbol 12-myristate 13-acetate PMCA, plasma membrane Ca2+-ATPase ROI, reactive oxygen intermediates SERCA, sarco/endoplasmic reticulum Ca2+-ATPase SKF-96365, 1-[β-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole SOCE, store-operated Ca2+ entry TCEP, tris-(2-carboxyethyl)phosphine U-73122, 1-[6-[17β-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|