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

P Strnad; M Siegel; Diana Toivola; K Choi; JC Kosek; C Khosla; MB Omary

doi:10.1016/j.febslet.2006.03.051

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

P Strnad
, M Siegel
, Diana Toivola
, K Choi
, JC Kosek
, C Khosla
, MB Omary

Biochemistry and Cell Biology

Research output: Contribution to journal › Article › Scientific › peer-review

15 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 NIB 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. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Original language	Undefined/Unknown
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
MoE publication type	A1 Journal article-refereed

Keywords

transglutaminase
Mallory body
keratin

Access to Document

10.1016/j.febslet.2006.03.051

Cite this

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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 NIB 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. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.",

keywords = "transglutaminase, Mallory body, keratin, transglutaminase, Mallory body, keratin, transglutaminase, Mallory body, keratin",

author = "P Strnad and M Siegel and Diana Toivola and K Choi and JC Kosek and C Khosla and MB Omary",

year = "2006",

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volume = "580",

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journal = "FEBS Letters",

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

AU - Strnad, P

AU - Siegel, M

AU - Toivola, Diana

AU - Choi, K

AU - Kosek, JC

AU - Khosla, C

AU - Omary, MB

PY - 2006

Y1 - 2006

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 NIB 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. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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 NIB 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. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

KW - transglutaminase

KW - Mallory body

KW - keratin

KW - transglutaminase

KW - Mallory body

KW - keratin

KW - transglutaminase

KW - Mallory body

KW - keratin

U2 - 10.1016/j.febslet.2006.03.051

DO - 10.1016/j.febslet.2006.03.051

M3 - Artikel

SN - 0014-5793

VL - 580

SP - 2351

EP - 2357

JO - FEBS Letters

JF - FEBS Letters

IS - 9

ER -