Reversal of decreased phosphorylation of sarcoplasmic reticulum calcium transport ATPase by 1,25-dihydroxycholecalciferol in experimental uremia
- 20 Downloads
When compared to that from shamoperated controls, sarcoplasmic reticulum isolated from skeletal muscle of uremic rabbits had a lower rate of calcium uptake and storing capacity. In vivo administration of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] restored the values in uremic animals toward normal. To obtain information about the mechanisms responsible for these differences, phosphorylation of the calcium transport ATPase was studied. The steady-state levels of phosphoprotein in uremic membranes were lower and returned to normal when the secosteroid was administered. Electrophoresis of the membranes phosphorylated with32P-inosine triphosphate (32P-ITP) showed that the differences were related to a 100,000 dalton protein. The rate of phosphoprotein formation, determined with32P-ITP and at 0°C, was considerably lower in uremic than in control animals. Pretreatment with 1,25(OH)2D3 prevented this change. The hypothesis is advanced that the vitamin D metabolite affects the steady-state concentration and rate constant of formation of active sites in the Ca-ATPase. These results may partly explain the altered Ca transport function of the sarcoplasmic reticulum in experimental uremia.
Key words1,25-Dihydroxycholecalciferol Uremia Muscle phosphorylation Sarcoplasmic reticulum ATPase
Unable to display preview. Download preview PDF.
- 6.Holmes AM, Enoch BA, Taylor JL, Jones ME (1973) Occult rickets and osteomalacia amongst the Asian immigrant population. Q J Med 42:125–149Google Scholar
- 9.Hasselbach W (1964) Relaxing factor and the relaxation of muscle. Prog Biophys Mol Chem 14:169–222Google Scholar
- 19.Zolock DT, Morrissey R., Bikle DD (1977) In: Norman AW et al. (eds) Vitamin D: Biochemical, chemical and clinical aspects related to calcium metabolism. Walter de Gruyter, New York, pp 345–347Google Scholar
- 20.Zolock DT, Morrisey RL, Bikle DD (1979) Meaning of nonparallel 1,25-dihydroxycholecalciferol mediated response relationship in intestine and bone to dose and time. In: Norman AW et al. (eds) Vitamin D—Basic research and its clinical application. Walter de Gruyter, New York, pp 639–642Google Scholar
- 22.Martonosi A (1979) Sarcoplasmic reticulum. VII. Properties of a phosphoprotein intermediate implicated in calcium transport. J Biol Chem 244:613–620Google Scholar
- 24.Kanazawa T, Yamada S, Tamnoto T, Tonomura Y (1971) Reaction mechanism of the Ca2+ dependent ATPase of sarcoplasmic reticulum from skeletal muscle. V. Vectorial requirements for calcium and magnesium ions of three partial reactions of ATPase: Formation and decomposition of a phosphorylated intermediate and ATP formation from ADP and the intermediate. J Biochem (Tokyo) 70:95–123Google Scholar
- 36.Schapira G, Dobocz I, Piau JP, Delain E (1974) An improved technique for preparation of skeletal muscle cell plasma membrane. Biochem Biophys Acta 345:348–358Google Scholar
- 46.Norman AW, Wecksler WR (1978) Receptors and hormone action. In: O'Malley BW, Birnbaumer L (eds) Vol II. Academic Press, New York, pp 533–571Google Scholar
- 49.Wasserman RH, Brindak ME (1979) The effect of cholecalciferol on the phosphorylation of intestinal membrane proteins. In: Norman AW et al (eds) Vitamin D—Basic research and its clinical application. De Gruyter, Berlin, pp 703–710Google Scholar
- 51.Peacock M, Heyburn PJ (1977) Effect of vitamin D metabolites on proximal muscle weakness (abstract). Calcif Tissue Res 24:R20Google Scholar