Functional changes of brain mitochondria during experimental hepatic encephalopathy

Dı́az-Muñoz, Mauricio; Tapia, Ricardo

doi:10.1016/0006-2952(89)90593-5

Cited by 15 publications

(7 citation statements)

References 30 publications

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“…Bessman and Bessman (1955) had suggested that excess ammonia might lead to a loss of ␣-ketoglutarate (a component of the TCA cycle) and NADH ϩ through its reductive amination to glutamate. Other mechanisms by which hyperammonemia could lead to energy failure include the inhibitory effect of ammonia on ␣-ketoglutarate dehydrogenase Díaz-Muñ oz and Tapia, 1989;Lai and Cooper, 1991), the rate limiting enzyme of the TCA cycle; the diversion of glutamate to glutamine by ammonia would deprive the astrocyte of an energy source as well as consume ATP; and the ammoniainduced stimulation of Na ϩ ,K ϩ -ATPase (Albrecht et al, 1985;Felipo et al, 1994;Sadasivudu et al, 1977;Ratnakumari et al, 1995) may also result in depletion of ATP. Additionally, ammonia impairs the astroglial oxidation of pyruvate and branched-chain amino acids (Fitzpatrick et al, 1988;Hertz et al, 1987;Murthy and Hertz, 1987) and glutamate Yu et al, 1984).…”

Section: Energy Metabolism In Hepatic Encephalopathy/hyperammonemiamentioning

confidence: 98%

The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: Relation to energy metabolism and glutamatergic neurotransmission

Norenberg

Huo

Neary

et al. 1997

Glia

135

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Abnormalities in glutamate metabolism and glutamatergic neurotransmission appear to play a major role in the pathogenesis of hyperammonemia and hepatic encephalopathy. Astrocytes may be involved in these derangements as ammonia has been shown to impair the ability of these cells to take up glutamate. This study presents a northern blot analysis of the GLT-1 glutamate transporter in hyperammonemic rats, and in rats with thioacetamide-induced acute liver failure. Our findings demonstrate a downregulation of GLT-1 mRNA in both conditions. This article examines the potential impact of deficits in glutamate uptake on energy metabolism and glutamatergic neurotransmission in the context of abnormalities in glial-neuronal interactions. We propose that an ammonia-induced abnormality in astroglial glutamate uptake constitutes a critical aspect in the pathogenesis of hepatic encephalopathy and other hyperammonemic conditions.

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Section: Energy Metabolism In Hepatic Encephalopathy/hyperammonemiamentioning

confidence: 98%

The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: Relation to energy metabolism and glutamatergic neurotransmission

Norenberg

Huo

Neary

et al. 1997

Glia

135

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“…It still remains to be established whether the changes represent a transition stage toward an ultrastructural damage characterizing more advanced or protracted hyperammonemic conditions. Therefore, this concept is difficult to reconcile with the report of Diaz-Munoz and Tapia (1989), who observed no changes in the distribution of the LDH and AChE activities in functionally impaired cerebral mitochondrial fractions derived from rats with hyperammonemia following protracted liver cirrhosis.…”

Section: Discussionmentioning

confidence: 51%

“…Numerous experimental studies with acute hyperammonemic models have demonstrated a rapid onset of changes in the brain oxygen metabolism and in a multitude of mitochondrial enzyme activities Murthy, 1983, 1985;Ratnakumari et al, 1986;Albrecht et al, 1987;Ratnakumari and Murthy, 1989). By contrast, profound changes in the ultrastructure or chemical structure (i.e., phospholipid or fatty acid composition) of mitochondria become apparent with a substantial delay, usually following chronic (several weeks) hyperammonemia or liver failure (Drewers and Leino, 1985;Diaz-Munoz and Tapia, 1989) or protracted treatment of cerebral tissue cultures with relatively high (>1 mM) concentrations of ammonium ions (Gregorios et al, 1985a,b;Hertz el al., 1987;Norenberg et al, 1991). In consequence, the links between the ammonia-induced functional changes and the structural impairment of the cerebral mitochondria remain elusive.…”

Section: Introductionmentioning

confidence: 99%

Changes in the cytoplasmic (lactate dehydrogenase) and plasma membrane (acetylcholinesterase) marker enzymes in the synaptic and nonsynaptic mitochondria derived from rats with moderate hyperammonemia

Faff-Michalak

Albrecht

1993

Molecular and Chemical Neuropathology

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The activities of the cytoplasmic and plasma membrane marker enzymes: lactate dehydrogenase (LDH) and acetylcholinesterase (AChE), respectively, were measured in the cerebral homogenates, in the synaptic and nonsynaptic mitochondrial fractions, and in the postmitochondrial supernatants derived from rats in which a 3-d, moderately hyperammonemic condition (no more than 120% increases in blood ammonia) was produced by repeated administration of ammonium acetate (simple hyperammonemia, SHA) or a hepatotoxin, thioacetamide (TAA) (hepatic encephalopathy, HE). As measured in the homogenate and postmitochondrial supernatants, neither of the enzyme activities was affected by SHA or HE. SHA and HE increased the synaptic mitochondrial LDH activity by respectively 53 and 24%, but reduced this enzyme activity in nonsynaptic mitochondria by 19%. Both conditions stimulated the synaptic and nonsynaptic mitochondrial AChE activity by 30-40%. By contrast, the only significant change produced in these fractions by in vitro treatment with a toxic (3 mM) concentration of ammonium chloride was a slight decrease of LDH activity in nonsynaptic mitochondria and postmitochondrial supernatants. It is concluded that moderate hyperammonemia modifies subsequent separation of both cerebral classes of mitochondria from the cytosolic and plasma membrane components. This modification is likely to reflect subtle hyperammonemia-related changes in the physicochemical properties of the two mitochondrial classes and/or other subcellular components.

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“…Tissue samples were obtained 2 hours after narcotization. Mitochondria were isolated from the medulla oblongata and frontal lobes of the cerebral hemispheres as described previously [13] in a medium containing 0.32 M sucrose, 10 mM Tris-HC1 (pH 7.4) and 1 mM EDTA [11]. The outer and inner mitochondrial membranes were isolated after Levy [12].…”

Section: Methodsmentioning

confidence: 99%

Changes in phospholipid composition of mitochondria in the medulla oblongata and frontal lobes of the cerebral hemispheres in hemorrhagic shock in cats

1996

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Considerable regional differences in the phospholipid composition of mitochondrial membranes are found in the brain of cats in the terminal phase of hemorrhagic shock. The most prominent alteration is noted in the medulla oblongata and consists in a progressive elimination of phosphatidylcholine. Changes in the main phospholipids in mitochondrial membranes of the cerebral hemispheres are less pronounced and consist in a drop of phosphatidylinositol and phosphatidylethanolamine. Accumulation of lysophosphatidylcholine and lysophosphatidylethanolamine is a regular feature of the studied mitochondria. Accumulation of lysophosphatidylserine is found primarily in mitochondrial membranes of the medulla oblongata.

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Functional changes of brain mitochondria during experimental hepatic encephalopathy

Cited by 15 publications

References 30 publications

The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: Relation to energy metabolism and glutamatergic neurotransmission

The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: Relation to energy metabolism and glutamatergic neurotransmission

Changes in the cytoplasmic (lactate dehydrogenase) and plasma membrane (acetylcholinesterase) marker enzymes in the synaptic and nonsynaptic mitochondria derived from rats with moderate hyperammonemia

Changes in phospholipid composition of mitochondria in the medulla oblongata and frontal lobes of the cerebral hemispheres in hemorrhagic shock in cats

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