Effect of exogenous and endogenous nitric oxide on mitochondrial respiration of rat hepatocytes

1991 ◽  
Vol 260 (5) ◽  
pp. C910-C916 ◽  
Author(s):  
J. Stadler ◽  
T. R. Billiar ◽  
R. D. Curran ◽  
D. J. Stuehr ◽  
J. B. Ochoa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Rat Hepatocytes ◽  
Significant Inhibition ◽  
Short Exposure ◽  
Aconitase Activity ◽  
Ubiquinone Oxidoreductase ◽  
Transport Chain ◽  
Mitochondrial Aconitase ◽  
Dependent Inhibition ◽  
Endogenous Nitric Oxide

Although nitric oxide (.N = O) biosynthesis is inducible in rat hepatocytes (HC), the physiological significance of .N = O production by these cells is unknown. Short exposure of HC to authentic .N = O led to a concentration-dependent inhibition of mitochondrial aconitase, NADH-ubiquinone oxidoreductase, and succinate-ubiquinone oxidoreductase (complexes I and II of the mitochondrial electron transport chain). Most susceptible to .N = O inhibition was mitochondrial aconitase, in which a reduction in enzyme activity to 20.2 +/- 1.6% of control was observed. In contrast to mitochondrial aconitase, cytosolic aconitase activity was not inhibited by .N = O. After exposure to a maximal inhibitory concentration of .N = O, mitochondrial aconitase activity recovered completely within 6 h. Complex I did not fully recover within this incubation period. Endogenous .N = O biosynthesis was induced in HC by a specific combination of cytokines and lipopolysaccharide. After 18 h of incubation with these stimuli, a significant inhibition of mitochondrial aconitase activity to 70.8 +/- 2.4% of controls was detected. However, this was due only in part to the action of .N = O. A non- .N = O-dependent inhibition of mitochondrial function appeared to be mediated by tumor necrosis factor.

Role of endogenous nitric oxide in progression of atherosclerosis in apolipoprotein E-deficient mice

2000 ◽  
Vol 278 (5) ◽  
pp. H1679-H1685 ◽  
Author(s):  
Katalin Kauser ◽  
Valdeci da Cunha ◽  
Richard Fitch ◽  
Cornell Mallari ◽  
Gabor M. Rubanyi
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Apolipoprotein E ◽  
Lesion Size ◽  
Significant Inhibition ◽  
Arterial Blood ◽  
Endogenous Nitric Oxide ◽  
Progression Of Atherosclerosis ◽  
Apoe Ko

This study investigated the role of endogenous nitric oxide (NO) in the progression of atherosclerosis in apolipoprotein E-deficient [apoE-knockout (KO)] mice. Mice were treated with N ω-nitro-l-arginine methyl ester (l-NAME) an inhibitor of nitric oxide synthase (NOS) or with the NOS substrate l-arginine for 8 wk.l-NAME treatment resulted in a significant inhibition of NO-mediated vascular responses and a significant increase in the atherosclerotic plaque/surface area in the aorta of apoE-KO mice.l-arginine treatment had no influence on endothelial function and did not alter lesion size. Mean arterial blood pressure and serum lipid levels were not altered by the treatments. At the beginning of the study impairment in endothelial function was only apparent in the case of N G-nitro-l-arginine-induced, NO-mediated contraction, whereas ACh-induced, NO-mediated relaxation was not different between age-matched apoE-KO and C57Bl/6J mice. After the 8-wk treatment with the NOS inhibitor, both NO-mediated responses were significantly inhibited. The acceleration in lesion size concomitant to the severely impaired NO-mediated responses indicates that lack of endogenous NO is an important progression factor of atherosclerosis in the apoE-KO mouse.

Role of endogenous nitric oxide in liver-specific functions and survival of cultured rat hepatocytes

Xenobiotica ◽  
2001 ◽  
Vol 31 (5) ◽  
pp. 249-264 ◽  
Author(s):  
M. T. Donato ◽  
X. Ponsoda ◽  
E. O’Connor ◽  
J. V. Castell ◽  
M. J. Gómez-Lechón
Keyword(s):  
Nitric Oxide ◽  
Rat Hepatocytes ◽  
Endogenous Nitric Oxide ◽  
Cultured Rat Hepatocytes

scholarly journals Role for c-Jun N-Terminal Kinase in β-Cell Recovery from Nitric Oxide-Mediated Damage

Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3415-3422 ◽  
Author(s):  
Anna L. Scarim ◽  
Sheri Y. Nishimoto ◽  
Sarah M. Weber ◽  
John A. Corbett
Keyword(s):  
Nitric Oxide ◽  
Insulin Secretion ◽  
Guanylate Cyclase ◽  
Recovery Process ◽  
Cell Recovery ◽  
Β Cells ◽  
Β Cell ◽  
No Donor ◽  
Aconitase Activity ◽  
Mitochondrial Aconitase

Abstract Treatment of rat islets with the cytokine IL-1 results in the inhibition of mitochondrial function and insulin secretion, events that are mediated by β-cell expression of iNOS [inducible nitric oxide (NO) synthase] and production of NO. β-Cells recover from the inhibitory actions of NO, produced following 24 h incubation with IL-1, on islet oxidative metabolism and insulin secretion if iNOS enzymatic activity is inhibited and the islets are cultured (in the presence of IL-1 and iNOS inhibitors) for a brief period of 8 h. Islet recovery from cytokine- and NO-mediated damage is an active process that requires new gene expression, and NO itself is one activator of this recovery process. In this study, the mechanism by which NO stimulates islet recovery has been examined. Incubation of rat islets or RINm5F cells with the NO donor compound, sodium (Z)-1(N,N-diethylamino) diazen-1-ium-1,2-diolate (DEA-NO) for 1 h results in a 60% inhibition of mitochondrial aconitase activity. β-Cells completely recover aconitase activity if the cells are washed to remove the NO donor compound and incubated for an additional 5 h in the absence of DEA-NO. The recovery of mitochondrial aconitase activity correlates with a 4-fold increase in cyclic GMP accumulation and is prevented by the inhibition of guanylate cyclase. The recovery of aconitase activity also correlates with the activation of members of the MAPKs, p38, c-Jun N-terminal kinase (JNK) and ERK, and the activation p38 and JNK is attenuated by inhibition of guanylate cyclase. ERK and p38 do not appear to participate in the recovery process as selective inhibition of these kinases fails to prevent recovery of aconitase activity; however, transduction of β-cells with a dominant negative mutant JNK prevents β-cell recovery from NO-mediated damage. These findings support a role for guanylate cyclase and JNK in the recovery of β-cells from NO-mediated damage.

Direct evidence of production of nitric oxide in the lipopolysaccharide-sensitized rat hepatocytes and kupffer cells

2001 ◽  
Vol 120 (5) ◽  
pp. A356-A356
Author(s):  
T KONO ◽  
J IWAMOTO ◽  
K ISHIKAWA ◽  
Y EBISAWA ◽  
T AOKI ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Kupffer Cells ◽  
Direct Evidence ◽  
Rat Hepatocytes
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