4.5 Article

M-30 and 4HNE are sequestered in different aggresomes in the same hepatocytes

Journal

EXPERIMENTAL AND MOLECULAR PATHOLOGY
Volume 83, Issue 3, Pages 296-300

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yexmp.2007.09.001

Keywords

caspase 3; oxidative stress; steatohepatitis; Mallory Denk bodies; aggresomes

Categories

Funding

  1. NIAAA NIH HHS [R01 AA014562-03, P50 AA011999, R01 AA014562, P50 AA011999-09] Funding Source: Medline
  2. PHS HHS [R01-014562, P50-011999] Funding Source: Medline

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M-30 and 4HNE adducts are two markers of active liver disease. M-30 is a serologic marker and 4HNE adducts are histologic markers. M-30 is a marker for apoptosis because it is a fragment of cytokeratin-18 left over from proteolysis by caspase 3. 4HNE is a marker of oxidative stress because it results from lipid peroxidation. Both markers are commonly found in nonalcoholic steatohepatitis and in alcoholic hepatitis. Liver biopsies from patients with steatohepatitis, 11 alcoholic and 11 non-alcoholics were stained for 4HNE and M-30. Almost all of the biopsies in both groups showed 4HNE- and M-30-positive aggresomes in hepatocytes. Mallory Denk bodies (MDB) stained variably positive for M-30, whereas 4HNE was present in aggresomes independent of MDBs. However, they were sometimes located in hepatocytes which also contained MDBs as shown by confocal microscopy of double stained biopsies. The results indicate that the formation of M-30 and 4HNE aggresomes occurs through different pathways of liver cell injury in both types of steatohepatitis. (c) 2007 Elsevier Inc. All rights reserved.

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