Isolation and characterization of coenzyme A glutathione disulfide as a parathyroid-derived vasoconstrictive factor
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Isolation and characterization of coenzyme A glutathione disulfide as a parathyroid-derived vasoconstrictive factor. / Jankowski, J; Schröter, A; Tepel, M; van der Giet, M; Stephan, N; Luo, J; Zidek, W; Schlüter, H.
in: CIRCULATION, Jahrgang 102, Nr. 20, 14.11.2000, S. 2548-52.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -