Isolation and characterization of coenzyme A glutathione disulfide as a parathyroid-derived vasoconstrictive factor

Article

关键词: SPONTANEOUSLY HYPERTENSIVE RATS;    VASCULAR SMOOTH-MUSCLE;    LASER-DESORPTION IONIZATION;    BLOOD-PRESSURE;    DIADENOSINE PHOSPHATES;    GLANDS;    RECEPTORS;    PEPTIDES;    CALCIUM;    GROWTH;   

DOI  :  10.1161/01.CIR.102.20.2548

来源: SCIE

【 摘 要 】

Background-Coenzyme A glutathione disulfide (CoA-SSG) was recently isolated from bovine adrenal glands and was shown to be a renal vasoconstrictor. The identification of CoA-SSG in human parathyroid glands and its action on cultured vascular smooth muscle cells (VSMCs) are described here. Methods and Results-After purification to homogeneity by several chromatographic steps, CoA-SSG was identified by matrix-assisted laser desorption/ionization mass spectrometry and enzymatic analysis. The dose-dependent growth-stimulating effect of CoA-SSG on VSMCs, measured by the [H-3]thymidine method, is characterized by a threshold of 10(-8) mol/L and a maximum effect of 10 mu mol/L, increasing VSMC proliferation 254+/-21% above control. A dose of 10 mu mol/L methylmalonyl-CoA and 10 mu mol/L CoA increased the rate of proliferation of VSMCs only by 178+/-43% and 50+/-42% above control. respectively. Glutathione has no proliferative effect on VSMCs. The growth-stimulating effect of CoA-SSG (1 mu mol/L) was decreased by the antagonists 3,7-dimethyl-1-propargylxanthine (DMPX; 11 mu mol/L) (38% compared with CoA-SSG without antagonist) and pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid (PPADS; 10 mu mol/L) (48% compared with CoA-SSG without antagonist; each P<0.05 versus control), indicating that the effect is mediated partly via A, and partly via P2Y1 and/or P2Y4 receptor. Conclusions-CoA-SSG may play a regulatory role in VSMC growth as a progression factor and thereby could play an important role in development of hypertension.

【 授权许可】

Free