These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Tumor necrosis factor alpha decreases inositol phosphate formation and phosphatidylinositol-bisphosphate (PIP2) synthesis in rat cardiomyocytes.
    Author: Reithmann C, Werdan K.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 1994 Feb; 349(2):175-82. PubMed ID: 8170501.
    Abstract:
    Treatment of neonatal rat cardiomyocytes for 72 h in the presence of tumor necrosis factor alpha (TNF alpha) (10 U/ml) lead to a decrease in basal and alpha 1-adrenoceptor-induced formation of the calcium-mobilizing second messenger inositol trisphosphate (IP3) and its metabolites, IP2 and IP1, by 35 and 26%, respectively. The synthesis of phosphatidylinositol bisphosphate (PIP2), the substrate of PI-specific phospholipase C, was decreased by 45% following the TNF alpha (10 U/ml) exposure. Time courses of TNF alpha (10 U/ml)-induced alterations in rat cardiomyocytes showed a parallel decline of basal inositol phosphate formation and PIP2 synthesis suggesting that the decrease in inositol phosphate formation was due to the reduction in PIP2 synthesis. As the TNF alpha-induced decrease of PIP2 synthesis was associated with a decreased synthesis of the phospholipid phosphatidylinositol (PI), the precursor of PIP2, by 33%, the decreased availability of PIP2 is apparently, at least in part, the result of the decreased synthesis of PI. As an apparent functional consequence of the decrease in IP3 formation following the TNF alpha exposure, the alpha 1-adrenoceptor-mediated induction of arrhythmias by 100 mumol/l noradrenaline + 10 mumol/l timolol was abolished in TNF alpha-pretreated rat cardiomyocytes. To investigate one of the possible mechanisms of the TNF alpha-induced decrease of PIP2 formation, the effect of TNF alpha pretreatment on glycerol-3-phosphate dehydrogenase (GDH), a key enzyme of lipogenesis, was studied: Exposure of the rat cardiomyocytes for 72 h to TNF alpha induced a concentration-dependent decrease in GDH activity by maximally 55%.(ABSTRACT TRUNCATED AT 250 WORDS)
    [Abstract] [Full Text] [Related] [New Search]