Modulation of Rat Liver Protein Kinase C during in Vivo CC14-Induced Oxidative Stress

Pronzato, M.A.; Domenicotti, Cinzia; Rosso, Enrico; Bellocchio, Antonella; Patrone, Mauro; Marinari, Umberto M.; Melloni, Edon; Poli, Giuseppe

doi:10.1006/bbrc.1993.1868

Cited by 31 publications

(9 citation statements)

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“…HNE-induced activation of PLC, at least in theory, should result in an increased production of inositol triphosphate (IP3) and diacylglycerol (DAG) within target cells exposed to the aldehyde. DAG is known to stimulate several protein kinase C (PKC) isoforms, and, indeed, exposure of isolated rat hepatocytes to low concentrations of HNE has been reported to lead to an increase in calcium-and phospholipid-dependent PKC detectable enzymatic activity (Pronzato et al, 1990(Pronzato et al, ,1993. In addition, very recently it has been shown that low doses of HNE may differentially modulate the expression of different PKC isoforms (Chiarpotto et al, 1999).…”

Section: -Hydroxynonenal As a Biological Signal In Pathophysiologymentioning

confidence: 99%

4-Hydroxynonenal As a Biological Signal: Molecular Basis and Pathophysiological Implications

Parola

Bellomo

Robino

et al. 1999

Antioxidants & Redox Signaling

237

171

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Reactive oxygen intermediates (ROI) and other pro-oxidant agents are known to elicit, in vivo and in vitro, oxidative decomposition of omega-3 and omega-6 polyunsaturated fatty acids of membrane phospholipids (i.e, lipid peroxidation). This leads to the formation of a complex mixture of aldehydic end-products, including malonyldialdehyde (MDA), 4-hydroxy-2,3-nonenal (HNE), and other 4-hydroxy-2,3-alkenals (HAKs) of different chain length. These aldehydic molecules have been considered originally as ultimate mediators of toxic effects elicited by oxidative stress occurring in biological material. Experimental and clinical evidence coming from different laboratories now suggests that HNE and HAKs can also act as bioactive molecules in either physiological and pathological conditions. These aldehydic compounds can affect and modulate, at very low and nontoxic concentrations, several cell functions, including signal transduction, gene expression, cell proliferation, and, more generally, the response of the target cell(s). In this review article, we would like to offer an up-to-date review on this particular aspect of oxidative stress--dependent modulation of cellular functions-as well as to offer comments on the related pathophysiological implications, with special reference to human conditions of disease.

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Section: -Hydroxynonenal As a Biological Signal In Pathophysiologymentioning

confidence: 99%

4-Hydroxynonenal As a Biological Signal: Molecular Basis and Pathophysiological Implications

Parola

Bellomo

Robino

et al. 1999

Antioxidants & Redox Signaling

237

171

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“…22 PKC is generally recognized as being involved in gene expression, cell proliferation, differentiation, and function, through a selective phosphorylating action of its various isoforms. 23,24 In previous research we described a significant stimulation of total Ca 2ϩ -dependent PKC in the liver of rats treated with a very low dose of carbon tetrachloride, a classic enhancer of lipid peroxidation and, as a consequence, of HNE formation 25 ; it appeared likely that a very low HNE tissue concentration would have a positive influence on cell function through up-regulation of specific PKC isoforms.…”

mentioning

confidence: 92%

Regulation of Rat Hepatocyte Protein Kinase C β Isoenzymes by the Lipid Peroxidation Product 4–Hydroxy–2,3–Nonenal: A Signaling Pathway to Modulate Vesicular Transport of Glycoproteins

et al. 1999

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A major aldehydic end product of the peroxidation of arachidonic acid, 4-hydroxy-2,3-nonenal (HNE), has recently been considered for its potential involvement in a variety of cell functions. Here we report on the differential regulation of rat hepatocyte protein kinase C (PKC) isoforms by concentrations of HNE actually detectable in specific biological fluids or tissues. PKC ␤I and, to a much greater extent, PKC ␤II activities were markedly increased by 0.1 mol/L HNE (final concentration in cell medium) whereas they were unaffected or even inhibited by 1 to 10 mol/L HNE. On the contrary, the calcium independent PKC ␦ activity was inhibited by 0.1 mol/L and increased by 1 and 10 mol/L. The carbonyl compound 4-hydroxy-2,3-nonenal (HNE) is one of the major products of the oxidative breakdown of -6 fatty acids, the featuring process of membrane lipid peroxidation. 1 This aldehyde, being strongly electrophylic, readily reacts at neutral or slightly alkaline pH with sulphydryl and amino groups. HNE production was quantified several years ago in rat liver microsomes and isolated hepatocytes undergoing various experimental conditions of enhanced lipid peroxidation. 2,3 In more recent in vivo experimental reproduction of liver 4 and arterial 5,6 fibrosclerotic lesions, the detectable steady-state HNE concentration reached the low-micromolar range, up to 5 to 10 µmol/L.Until rather recently, in vitro biochemical studies were oriented towards seeking evidence of the many biochemical effects of HNE, generally using concentrations above 10 µmol/L; these were normally performed by adding the aldehyde to cell cultures or suspensions or cellular subfractions. 1 Such an approach was adopted to counteract the high aldehyde metabolism shown by the majority of the cell types tested 7 ; however, it directed the investigation to quantities of HNE of rather unlikely biological interest. Further, the overall negative effects exerted by relatively high HNE dosage contributed to the short-sighted opinion that this and related lipid peroxidation products were simply detrimental and acutely toxic to cells and tissues and consequently were of limited interest in pathophysiology.This state of affairs was rectified in particular by extensive research on the role of oxidatively modified low density lipoproteins in the pathogenesis of atherosclerosis 8 and the detection in the human plasma of autoantibodies against HNE-modified low-density lipoproteins 9 or of HNE-modified proteins, 10 and a role of HNE in pathophysiology became more favorably considered.At present, because of the use of specific monoclonal antibodies raised against tissue HNE-protein adducts, the number of human diseases with detectable accumulation of HNE is rapidly growing: increased HNE levels have been recognized in the liver of patients with alcohol-induced Abbreviations: HNE, 4-hydroxy-2,3-nonenal; PKC, protein kinase C; CD, cathepsin D; DAG, diacylglycerol.From the

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“…Protein kinase C can be activated by oxidants like H202 and PV however certain oxidative conditions inactivate PKC (9,10), and thus its SIGNAL TRANSDUCTION I N SMOOTH MUSCLE CELLS involvement in downstream signaling is controversial. Different methods to assess the role of PKC in oxidant-induced signal transduction have also given conflicting results, e.g., in ischemic preconditioning of the myocardium and in regulation of cellular permeability (11,12).…”

Section: Introductionmentioning

confidence: 99%

Redox Regulation of Signal Transduction in Smooth Muscle Cells: Distinct effects of PKC-down regulation and PKC inhibitors on oxidant induced MAP kinase

Taher

Mahgoub

Abd‐Elfattah

1998

Journal of Receptors and Signal Transduction

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Reactive oxygen species function as signaling molecules, and are known to be generated under both normal and pathological conditions. Using vascular smooth muscle cells, we have demonstrated an increase in mitogen activated protein kinase activity in response to oxidants. Mitogen activated protein kinase activity increased linearly with time in cells treated with pervanadate. Hydrogen peroxide also caused rapid induction of mitogen activated protein kinase. Protein kinase C down regulation partially decreased induction of mitogen activated protein kinase activity by oxidants, and the Ca2+ ionophore, ionomycin. Protein kinase C inhibitors, compound-3 and bisindolylmaleimide did not inhibit oxidant induced mitogen activated protein kinase activity, where as calphostin C activated it. The tyrosine kinase inhibitors genistein, herbimycin A and tyrphostin caused 50% inhibition of oxidant induced mitogen activated protein kinase activation. These results suggest that oxidant-induced mitogen activated protein kinase is protein kinase C independent.

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Modulation of Rat Liver Protein Kinase C during in Vivo CC14-Induced Oxidative Stress

Cited by 31 publications

References 0 publications

4-Hydroxynonenal As a Biological Signal: Molecular Basis and Pathophysiological Implications

4-Hydroxynonenal As a Biological Signal: Molecular Basis and Pathophysiological Implications

Regulation of Rat Hepatocyte Protein Kinase C β Isoenzymes by the Lipid Peroxidation Product 4–Hydroxy–2,3–Nonenal: A Signaling Pathway to Modulate Vesicular Transport of Glycoproteins

Redox Regulation of Signal Transduction in Smooth Muscle Cells: Distinct effects of PKC-down regulation and PKC inhibitors on oxidant induced MAP kinase

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