Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
1991-8-7
pubmed:abstractText
The mechanisms underlying agonist-induced oscillations in intracellular free calcium ion concentration ([Ca2+]i) in hepatocytes were investigated by utilizing tert-butyl hydroperoxide (TBHP) as a tool to perturb hepatocyte Ca2+ homeostasis independent of receptor activation. In permeabilized hepatocytes, TBHP inhibited Ca2+ uptake into the inositol 1,4,5-trisphosphate (InsP3)-sensitive Ca2+ pool and increased the sensitivity to InsP3 for Ca2+ release. The effects of TBHP could be mimicked by addition of oxidized glutathione (GSSG) and reversed by pretreatment with dithiothreitol. TBHP and GSSG had no effect on the metabolic degradation of [3H]InsP3 in permeabilized cells. The effect of TBHP on [Ca2+]i in intact cells was investigated by digital imaging fluorescence microscopy of Fura-2-loaded primary cultured hepatocytes. TBHP treatment initiated a series of [Ca2+]i oscillations similar to those caused by Ca2(+)-mobilizing hormones. Moreover, in common with the actions of hormones in these cells (Rooney, T.A., Sass, E., and Thomas, A,P. (1990) J. Biol. Chem. 265, 10792-10796), the [Ca2+]i oscillations induced by TBHP propagated through the cell as Ca2+ waves, originating from a discrete subcellular locus identical to that for phenylephrine-induced [Ca2+]i oscillations. The Ca2+ waves induced by TBHP had similar rates of progress (24-27 microns.s-1) to those generated by phenylephrine. Removal of extracellular Ca2+ increased the initial latency of the TBHP responses, but had no effect on the amplitude or rate of propagation of the Ca2+ waves. Addition of TBHP to cells in the presence of phenylephrine converted the oscillatory phenylephrine [Ca2+]i response into a sustained [Ca2+]i increase. The effects of TBHP in intact cells occurred in the absence of any stimulated inositol polyphosphate formation as measured in populations of [3H]inositol-labeled hepatocytes. The data indicate that spatially organized [Ca2+]i oscillations in intact hepatocytes can occur without any requirement for phospholipase C activation. Furthermore, for agents that act by mobilizing Ca2+ from the InsP3-sensitive pool, the kinetics of the Ca2+ release phase of the [Ca2+]i oscillations appears to be independent of the nature of the stimulus.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
266
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12272-82
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:2061312-Animals, pubmed-meshheading:2061312-Calcium, pubmed-meshheading:2061312-Enzyme Activation, pubmed-meshheading:2061312-Fura-2, pubmed-meshheading:2061312-Glutathione, pubmed-meshheading:2061312-Homeostasis, pubmed-meshheading:2061312-Inositol 1,4,5-Trisphosphate, pubmed-meshheading:2061312-Liver, pubmed-meshheading:2061312-Male, pubmed-meshheading:2061312-Membrane Potentials, pubmed-meshheading:2061312-Oxidation-Reduction, pubmed-meshheading:2061312-Peroxides, pubmed-meshheading:2061312-Phenylephrine, pubmed-meshheading:2061312-Plant Extracts, pubmed-meshheading:2061312-Rats, pubmed-meshheading:2061312-Rats, Inbred Strains, pubmed-meshheading:2061312-Terpenes, pubmed-meshheading:2061312-Thapsigargin, pubmed-meshheading:2061312-Type C Phospholipases, pubmed-meshheading:2061312-tert-Butylhydroperoxide
pubmed:year
1991
pubmed:articleTitle
Oscillatory cytosolic calcium waves independent of stimulated inositol 1,4,5-trisphosphate formation in hepatocytes.
pubmed:affiliation
Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't