sja-6017 and Acidosis

sja-6017 has been researched along with Acidosis* in 1 studies

Other Studies

1 other study(ies) available for sja-6017 and Acidosis

ArticleYear
Phosphoinositide 3-kinase accelerates calpain-dependent proteolysis of fodrin during hypoxic cell death.
    Journal of biochemistry, 2002, Volume: 132, Issue:6

    We have shown recently that phosphoinositide 3-kinase (PI 3-kinase) accelerates the hypoxia-induced necrotic cell death of H9c2, derived from rat cardiomyocytes, by enhancing metabolic acidosis. Here we show the downstream events of acidosis that cause hypoxic cell death. Hypoxia induces the proteolysis of fodrin, a substrate of calpain. Intracellular Ca(2+) chelation by BAPTA, and the addition of SJA6017, a specific peptide inhibitor of calpain, also reduces cell death and fodrin proteolysis, indicating that Ca(2+) influx and calpain activation might be involved in these events. The overexpression of wild type PI 3-kinase accelerates fodrin proteolysis, while dominant-negative PI 3-kinase reduces it. Both (N-ethyl-N-isopropyl)amiloride (EIPA), an inhibitor of the Na(+)/H(+) exchanger, and KB-R7943, an inhibitor of the Na(+)/Ca(2+) exchanger, reduce hypoxic cell death and fodrin proteolysis. The depletion of intracellular Ca(2+ )stores by thapsigargin, an inhibitor of endoplasmic reticulum Ca(2+)-ATPase, also reduces cell death and fodrin proteolysis, indicating that Ca(2+ )release from intracellular Ca(2+ )stores might be also involved. These results indicate that PI 3-kinase might accelerate hypoxic cell death by enhancing the calpain-dependent proteolysis of fodrin.

    Topics: Acidosis; Animals; Antimetabolites; Buffers; Calcium; Calcium-Transporting ATPases; Calpain; Cell Death; Cell Hypoxia; Cell Survival; Cells, Cultured; Chelating Agents; Deoxyglucose; Dipeptides; Egtazic Acid; Enzyme Activation; Enzyme Inhibitors; Gene Transfer Techniques; HEPES; Myocytes, Cardiac; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Rats; Sodium-Calcium Exchanger; Sodium-Hydrogen Exchangers

2002