We have examined the effects in vitro of calcitriol [1,25(OH)2D3], the hormonal form of vitamin D3, on the breakdown of membrane phosphoinositides in skeletal muscle from young (3 months) and aged (24 months) rats. Calcitriol (10(-9) M) induced a rapid and transient release of IP3/inositol phosphates and diacylglycerol (DAG) from muscle slices/membranes prelabeled with [3H]myo-inositol and [3H]arachidonate, respectively. Inositol phosphate release was maximal at 15 s and then declined. The effects of hormone specificity exhibited as the closely related derivatives of vitamin D3, 25OHD3, 1alphaOHD3 and 24,25(OH)2D3 did not alter muscle inositol phosphate levels. The stimulation of DAG was biphasic, the early phase (15 s) being abolished by neomycin (0.5 mM), an inhibitor of phosphoinositide hydrolysis, similar to IP3 formation and consistent with a role of phospholipase C (PLC) in intracellular signal generation. Neomycin had no effect on the second DAG peak (2 min) induced by calcitriol, suggesting that the late phase of DAG formation is independent from the hydrolysis of phosphoinositides. Higher basal inositol phosphate and DAG levels were detected in muscle from aged rats thereby reducing the effects of the hormone on second messenger generation ( -80 and -60% for IP3 and DAG, respectively). Calcitriol stimulation of PLC was mimicked, in both young and old rats, by GTPgammaS, a non-hydrolyzable analogue of GTP, while GDPbetaS, a G protein inhibitor, suppressed the effect of the hormone. The early effects of calcitriol and GTPgammaS were not additive. Bordetella pertussis toxin abolished by 85% the effects of calcitriol on inositol phosphate release in young rats but was without effect in aged animals. These results demonstrate that calcitriol activates phosphoinositide-PLC in rat skeletal muscle by a mechanism which involves a pertussis-sensitive G protein and that the effects of the hormone are altered with ageing.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0303-7207(97)00221-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
In silico identification of a phosphate marine steroid from Indonesian marine compounds as a potential inhibitor of phosphatidylinositol mannosyltransferase (PimA) in Mycobacterium tuberculosis.
Comput Biol Med
January 2025
Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia; Drug Development Study Centre, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia.
A higher death rate is associated with multiple factors, including medication resistance and co-infection with the human immunodeficiency virus (HIV). This shows the need to obtain new and effective drug candidates in improving tuberculosis (TB) treatment. In addition, the phosphatidylinositol mannosyltransferase (PimA) enzyme starts the production of phosphatidyl-myo-inositol.
View Article and Find Full Text PDFStructural mechanism underlying PHO1;H1-mediated phosphate transport in Arabidopsis.
Nat Plants
January 2025
National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.
Arabidopsis PHOSPHATE 1 (AtPHO1) and its closest homologue AtPHO1;H1 are phosphate transporters that load phosphate into the xylem vessel for root-to-shoot translocation. AtPHO1 and AtPHO1;H1 are prototypical members of the unique SPX-EXS family, whose structural and molecular mechanisms remain elusive. In this study, we determined the cryogenic electron microscopy structure of AtPHO1;H1 binding with inorganic phosphate (Pi) and inositol hexakisphosphate in a closed conformation.
View Article and Find Full Text PDFModulation of the Oxygenation State and Intracellular pH of Erythrocytes by Inositol-Trispyrophosphate Investigated by P NMR Study of 2,3-DPG.
J Cell Mol Med
January 2025
Centre for Molecular Biophysics, UPR CNRS 4301, Orleans, France.
The hypoxic microenvironment is crucial for tumour cell growth and invasiveness. Tumour tissue results from adaptation to reduced oxygen availability. Hypoxia first activates pro-angiogenic signals for alleviation.
View Article and Find Full Text PDFTranscriptional activation and coactivator binding by yeast Ino2 and human proto-oncoprotein c-Myc.
Curr Genet
January 2025
Center for Functional Genomics of Microbes, Institut Für Genetik Und Funktionelle Genomforschung, Universität Greifswald, Felix-Hausdorff-Straße 8, 17487, Greifswald, Germany.
Basic helix-loop-helix domains in yeast regulatory proteins Ino2 and Ino4 mediate formation of a heterodimer which binds to and activates expression of phospholipid biosynthetic genes. The human proto-oncoprotein c-Myc (Myc) and its binding partner Max activate genes important for cellular proliferation and contain functional domains structure and position of which strongly resembles Ino2 and Ino4. Since Ino2-Myc and Ino4-Max may be considered as orthologs we performed functional comparisons in yeast.
View Article and Find Full Text PDFStructural basis of phosphate export by human XPR1.
Nat Commun
January 2025
Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, China.
Phosphorus in crucial for all living organisms. In vertebrate, cellular phosphate homeostasis is partly controlled by XPR1, a poorly characterized inositol pyrophosphate-dependent phosphate exporter. Here, we report the cryo-EM structure of human XPR1, which forms a loose dimer with 10 transmembrane helices (TM) in each protomer.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!