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

TY - JOUR

T1 - Isolation and characterization of coenzyme A glutathione disulfide as a parathyroid-derived vasoconstrictive factor

AU - Jankowski, J

AU - Schröter, A

AU - Tepel, M

AU - van der Giet, M

AU - Stephan, N

AU - Luo, J

AU - Zidek, W

AU - Schlüter, H

PY - 2000/11/14

Y1 - 2000/11/14

N2 - 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 [(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.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.

AB - 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 [(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.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.

KW - Acetates

KW - Angiotensin II

KW - Animals

KW - Cell Division

KW - Cells, Cultured

KW - Chromatography, High Pressure Liquid

KW - Chromatography, Ion Exchange

KW - Coenzyme A

KW - Disulfides

KW - Dose-Response Relationship, Drug

KW - Glutathione

KW - Humans

KW - Mercaptoethanol

KW - Molecular Weight

KW - Muscle, Smooth, Vascular

KW - Parathyroid Glands

KW - Purinergic P1 Receptor Antagonists

KW - Purinergic P2 Receptor Antagonists

KW - Pyridoxal Phosphate

KW - Rats

KW - Rats, Inbred WKY

KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

KW - Theobromine

KW - Vasoconstrictor Agents

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - SCORING: Journal article

C2 - 11076831

VL - 102

SP - 2548

EP - 2552

JO - CIRCULATION

JF - CIRCULATION

SN - 0009-7322

IS - 20

ER -