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

doi:10.1016/j.febslet.2006.03.051

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 journal › Article › peer-review

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 language	English
Pages (from-to)	2351-2357
Number of pages	7
Journal	FEBS Letters
Volume	580
Issue number	9
DOIs	https://doi.org/10.1016/j.febslet.2006.03.051
Publication status	Published - 2006 Apr 17
Externally published	Yes

Keywords

Keratin
Mallory body
Transglutaminase

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2006.03.051

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@article{40a4a77eae534eabb26887ad14633193,

title = "Pharmacologic transglutaminase inhibition attenuates drug-primed liver hypertrophy but not Mallory body formation",

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.",

keywords = "Keratin, Mallory body, Transglutaminase",

author = "Pavel Strnad and Matthew Siegel and Toivola, {Diana M.} and Kihang Choi and Kosek, {Jon C.} and Chaitan Khosla and Omary, {M. Bishr}",

note = "Funding Information: We are grateful to Evelyn Resurrection for assistance with immunofluorescence staining. This work was supported by National Institutes of Health (NIH) Grant DK52951 and the Department of Veterans Affairs (M.B.O.), NIH Grant DK063198 (C.K.), Digestive Disease Center NIH Grant DK56339 and a European Molecular Biology Organization postdoctoral fellowship (P.S.).",

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doi = "10.1016/j.febslet.2006.03.051",

language = "English",

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T1 - Pharmacologic transglutaminase inhibition attenuates drug-primed liver hypertrophy but not Mallory body formation

AU - Strnad, Pavel

AU - Siegel, Matthew

AU - Toivola, Diana M.

AU - Choi, Kihang

AU - Kosek, Jon C.

AU - Khosla, Chaitan

AU - Omary, M. Bishr

N1 - Funding Information: We are grateful to Evelyn Resurrection for assistance with immunofluorescence staining. This work was supported by National Institutes of Health (NIH) Grant DK52951 and the Department of Veterans Affairs (M.B.O.), NIH Grant DK063198 (C.K.), Digestive Disease Center NIH Grant DK56339 and a European Molecular Biology Organization postdoctoral fellowship (P.S.).

PY - 2006/4/17

Y1 - 2006/4/17

N2 - 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.

AB - 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.

KW - Keratin

KW - Mallory body

KW - Transglutaminase

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DO - 10.1016/j.febslet.2006.03.051

M3 - Article

C2 - 16616523

AN - SCOPUS:33645988884

SN - 0014-5793

VL - 580

SP - 2351

EP - 2357

JO - FEBS Letters

JF - FEBS Letters

IS - 9

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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