Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-7-9
pubmed:abstractText
Interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) are produced by hepatic nonparenchymal cells after systemic injury and have been reported to inhibit ATP synthesis in hepatocytes, which may contribute to hepatic dysfunction in inflammatory states. To elucidate the mechanisms of action of IL-1beta and IL-6 on hepatocellular ATP synthesis, we measured the oxygen uptake rate (OUR) and mitochondrial membrane potential (MMP) of stable hepatocyte cultures, and analyzed the dynamic MMP response following the addition of mitochondrial inhibitors (antimycin A and oligomycin) with a model of mitochondrial metabolism. IL-1beta reduced mitochondrial OUR coupled to ATP synthesis via inhibition of phosphorylation reactions which dissipate the MMP, including ATP synthesis and consumption. Furthermore, the ATP synthesis rate in cytokine-free and IL-1beta-treated hepatocytes was controlled primarily by phosphorylation reactions, which corresponds to a state where the ATP synthesis rate closely follows the cellular energy demand. Thus, IL-1beta-mediated effects on electron transport and substrate oxidation reactions are not likely to significantly impact on ATP synthesis. IL-6 did not reduce mitochondrial OUR coupled to ATP synthesis, but shifted the control for ATP synthesis towards processes which generate the MMP, indicating that IL-6 induces a metabolic state where cellular functions are limited by the mitochondrial energy supply.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1096-7176
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
108-23
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Control analysis of mitochondrial metabolism in intact hepatocytes: effect of interleukin-1beta and interleukin-6.
pubmed:affiliation
Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Evaluation Studies, Validation Studies