Inactivation of protein kinase C in rat liver during late hypoglycemic phase of sepsis |
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Authors: | Hsu Chin Jao Hsiao-Ching Yang Shaw-Lang Hsu Hseng-Kuang Liu Maw-Shung |
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Affiliation: | (1) Department of Physiology, Graduate Institute of Medicine, Kaohsiung Medical College, Kaohsiung, Taiwan;(2) Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA |
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Abstract: | Changes in protein kinase C (PKC) (calcium- and phospholipid-dependent protein kinase) activity in rat liver during different metabolic phases of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). Experiments were divided into three groups: control, early sepsis, and late sepsis. Early and late sepsis refers to those animals sacrificed at 9 and 18 h, respectively, after CLP. Hepatic PKC was extracted and partially purified by ammonium sulfate fractionation and DEAE-cellulose chromatography. PKC activity was assayed based on the rate of incorporation of 32p from [-32P]ATP into histone. The results show that during early sepsis, both membrane-associated and cytosolic PKC activities remained relatively unaltered. During late sepsis, membrane-associated PKC was unaffected while cytosolic PKC activity was decreased by 19.5-34.4%. Kinetic analysis of the data on cytosolic PKC during late phase of sepsis reveals that the Vmax values for ATP, histone, Ca2+, phosphatidylserine, and diacylglycerol were decreased by 23.4, 22.1, 19.5, 25, and 34.4%, respectively, with no changes in their Km values. These data indicate that cytosolic PKC activity was inactivated in rat liver during late hypoglycemic phase of sepsis. Since PKC-mediated phosphorylation plays an important role in regulating hepatic glucose metabolism, an inactivation of cytosolic PKC may contribute to the development of hypoglycemia during late phase of sepsis. |
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Keywords: | protein kinase C calcium- and phospholipid-dependent protein kinase kinase mediated phosphorylation glucose dyshomeostasis hypoglycemia sepsis septic shock rat liver |
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