Glutamate cysteine ligase up-regulation fails in necrotizing pancreatitis.

Glutamate cysteine ligase up-regulation fails in necrotizing pancreatitis. Research Abstract Details 

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Glutamate cysteine ligase up-regulation fails in necrotizing pancreatitis. Abstract Text:

Javier Pereda,Javier Escobar,Juan Sandoval, ,Luis Sabater,Federico V ,Luis Torres,Luis Franco, ,Gerardo ,Juan Sastre,

Glutathione depletion is a key factor in the development of acute pancreatitis. Our aim was to study the regulation of glutamate cysteine ligase, the rate-limiting enzyme in glutathione synthesis, in edematous or necrotizing pancreatitis in rats. Glutathione levels were kept low in necrotizing pancreatitis for several hours, with no increase in protein or mRNA levels of glutamate cysteine ligase subunits, despite binding of RNA polymerase II to their promoters and coding regions. The survival signal pathway mediated by ERK and c-MYC was activated, and c-MYC was recruited to the promoters. The failure in gene up-regulation seems to be due to a marked increase in cytosolic ribonuclease activity. In contrast, in edematous pancreatitis glutathione levels were depleted and rapidly restored, and protein and mRNA expression of glutamate cysteine ligase increased markedly due to enhanced transcription mediated by recruitment of c-MYC, NF-kappaB, and SP-1 to the promoters. No increase in cytosolic ribonuclease activity was found in this case. We propose a novel pathophysiological mechanism to differentiate necrotizing from edematous pancreatitis, which is the inefficient up-regulation of glutamate cysteine ligase caused by increased cytosolic ribonuclease activity in the severe form of the disease. This mechanism would abrogate a rapid recovery of glutathione levels.

Glutamate cysteine ligase up-regulation fails in necrotizing pancreatitis. Publishing Authors By Initials

J Pereda,J Escobar,J Sandoval,JL ,L Sabater,FV ,L Torres,L Franco,J ,G ,J Sastre,

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Glutamate cysteine ligase up-regulation fails in necrotizing pancreatitis. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Free radical biology & medicine

VOLUME: 44

Page Numbers: 1599-609

Journal Abbreviation: Free Radic. Biol. Med.

ISSN: 0891-5849

DAY: 31

MONTH: 01

YEAR: 2008

Glutamate cysteine ligase up-regulation fails in necrotizing pancreatitis. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Glutamate cysteine ligase up-regulation fails in necrotizing pancreatitis.

AFFILIATION: Department of Physiology, University of Valencia, 46100 Burjasot (Valencia), Spain.

Country: United States

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MEDLINETA: Free Radic Biol Med

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