Pharmacologic transglutaminase inhibition attenuates drug-primed liver hypertrophy but not Mallory body formation

Pavel Strnad, Matthew Siegel, Diana M. Toivola, Kihang Choi, Jon C. Kosek, Chaitan Khosla, M. Bishr Omary

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Mallory bodies (MBs) are characteristic of several liver disorders, and consist primarily of keratins with transglutaminase-generated keratin crosslinks. We tested the effect of the transglutaminase-2 (TG2) inhibitor KCC009 on MB formation in a mouse model fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). KCC009 decreased DDC-induced liver enlargement without affecting MB formation or extent of liver injury. TG2 protein and activity increased after DDC feeding and localized within and outside hepatocytes. KCC009 inhibited DDC-induced hepatomegaly by affecting hepatocyte cell size rather than proliferation. Hence, TG2 is a potential mediator of injury-induced hepatomegaly via modulation of hepatocyte hypertrophy, and KCC009-mediated TG2 inhibition does not affect mouse MB formation.

Original languageEnglish
Pages (from-to)2351-2357
Number of pages7
JournalFEBS Letters
Volume580
Issue number9
DOIs
Publication statusPublished - 2006 Apr 17
Externally publishedYes

Fingerprint

Mallory Bodies
Transglutaminases
Liver
Hypertrophy
Hepatocytes
Hepatomegaly
Keratins
Pharmaceutical Preparations
Wounds and Injuries
Cell Size
Modulation
KCC 009
transglutaminase 2
Proteins

Keywords

  • Keratin
  • Mallory body
  • Transglutaminase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Pharmacologic transglutaminase inhibition attenuates drug-primed liver hypertrophy but not Mallory body formation. / Strnad, Pavel; Siegel, Matthew; Toivola, Diana M.; Choi, Kihang; Kosek, Jon C.; Khosla, Chaitan; Omary, M. Bishr.

In: FEBS Letters, Vol. 580, No. 9, 17.04.2006, p. 2351-2357.

Research output: Contribution to journalArticle

Strnad, Pavel ; Siegel, Matthew ; Toivola, Diana M. ; Choi, Kihang ; Kosek, Jon C. ; Khosla, Chaitan ; Omary, M. Bishr. / Pharmacologic transglutaminase inhibition attenuates drug-primed liver hypertrophy but not Mallory body formation. In: FEBS Letters. 2006 ; Vol. 580, No. 9. pp. 2351-2357.
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