@entity99 ( @entity99 ) is an important cause of morbidity and mortality in @entity1 with severe @entity409 . Although the mechanisms responsible for @entity99 remain elusive, @entity3265 is generally considered to be involved in its pathogenesis, and astrocytes are thought to be the principal target of @entity3265 @entity2359 . Altered bioenergetics and oxidative stress are also thought to play a major role in this disorder. In this paper, we present data invoking the mitochondrial permeability transition (MPT) as a factor in the pathogenesis of @entity99 / @entity3263 . The MPT is a @entity141 -dependent, @entity205 (CsA) sensitive process due to the opening of a pore in the inner mitochondrial membrane that leads to a collapse of ionic gradients and ultimately to @entity2383 . Many of the factors that facilitate the induction of the MPT are also known to be implicated in the mechanism of @entity99 , including free radicals, @entity141 , @entity842 , alkaline pH, and @entity1160 . We have recently shown that treatment of cultured astrocytes with 5 mM @entity8777 resulted in a dissipation of the mitochondrial membrane potential (delta(psi)m), which was sensitive to CsA. Similarly treated cultured neurons failed to show a loss of the delta(psi)m. Further support for the @entity3265 induction of the MPT was obtained by observing an increase in mitochondrial permeability to @entity36262 , and a decrease in calcein fluorescence in astrocytes after @entity3265 treatment, both of which were also blocked by CsA. CsA was likewise capable of exerting a protective effect against @entity3263 in @entity19 . Taken together, our data suggest that the MPT represents an important component of the pathogenesis of @entity99 and other hyperammonemic states.

XXXX @entity2359 : role of the mitochondrial permeability transition.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity8777 :: ('CHEBI:31206', 'Chemical') :: ['NH4Cl'] @entity1160 :: ('CHEBI:28300', 'Chemical') :: ['glutamine'] @entity3265 :: ('MESH:D000641', 'Chemical') :: ['ammonia'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity409 :: ('MESH:D008107', 'Disease') :: ['liver disease'] @entity3263 :: ('MESH:D022124', 'Disease') :: ['hyperammonemia'] @entity205 :: ('MESH:D016572', 'Chemical') :: ['cyclosporin A'] @entity36262 :: ('MESH:C015785', 'Chemical') :: ['2-deoxyglucose-6-phosphate'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+'] @entity99 :: ('MESH:D056486', 'Disease') :: ['Hepatic encephalopathy', 'HE'] @entity2359 :: ('MESH:D020258', 'Disease') :: ['neurotoxicity'] @entity2383 :: ('MESH:D028361', 'Disease') :: ['mitochondrial dysfunction']
@entity3265 :: (MESH:D000641,Chemical) :: ['Ammonia']
