Jankowski J, Schröter A, Tepel M, van der Giet M, Stephan N, Luo J, Zidek W, Schlüter H
Medizinische Klinik I, Universitäts-Klinik Marienhospital, Ruhr University of Bochum, Germany.
Circulation. 2000 Nov 14;102(20):2548-52. doi: 10.1161/01.cir.102.20.2548.
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.
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 [(3)H]thymidine method, is characterized by a threshold of 10(-)(8) mol/L and a maximum effect of 10 micromol/L, increasing VSMC proliferation 254+/-21% above control. A dose of 10 micromol/L methylmalonyl-CoA and 10 micromol/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 micromol/L) was decreased by the antagonists 3,7-dimethyl-1-propargylxanthine (DMPX; 11 micromol/L) (38% compared with CoA-SSG without antagonist) and pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid (PPADS; 10 micromol/L) (48% compared with CoA-SSG without antagonist; each P:<0. 05 versus control), indicating that the effect is mediated partly via A(2) and partly via P(2)Y(1) and/or P(2)Y(4) receptor.
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.
辅酶A谷胱甘肽二硫化物（CoA-SSG）最近从牛肾上腺中分离出来，并被证明是一种肾血管收缩剂。本文描述了CoA-SSG在人甲状旁腺中的鉴定及其对培养的血管平滑肌细胞（VSMC）的作用。
经多个色谱步骤纯化至同质后，通过基质辅助激光解吸/电离质谱和酶分析鉴定出CoA-SSG。用[³H]胸苷法测定，CoA-SSG对VSMC的剂量依赖性生长刺激作用的特征为阈值为10⁻⁸mol/L，最大效应为10μmol/L，使VSMC增殖比对照增加254±21%。10μmol/L的甲基丙二酰辅酶A和10μmol/L的辅酶A剂量分别仅使VSMC的增殖率比对照增加178±43%和50±42%。谷胱甘肽对VSMC没有增殖作用。拮抗剂3,7-二甲基-1-炔丙基黄嘌呤（DMPX；11μmol/L）（与无拮抗剂的CoA-SSG相比降低38%）和磷酸吡哆醛-6-偶氮苯基-2,4-二磺酸（PPADS；10μmol/L）（与无拮抗剂的CoA-SSG相比降低48%；与对照相比，各P<0.05）可降低CoA-SSG（1μmol/L）的生长刺激作用，表明该作用部分通过A₂部分通过P₂Y₁和/或P₂Y₄受体介导。
CoA-SSG可能作为一种进展因子在VSMC生长中起调节作用，从而可能在高血压的发生发展中起重要作用。
