c-Jun Terminal Kinase-2 Gene Deleted Mice Overexpress Hemeoxygenase-1 and Are Protected From Hepatic Ischemia Reperfusion Injury

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c-Jun Terminal Kinase-2 Gene Deleted Mice Overexpress Hemeoxygenase-1 and Are Protected From Hepatic Ischemia Reperfusion Injury. / Devey, L; Mohr, Elodie; Bellamy, C; Simpson, K; Henderson, N; Harrison, EM; Ross, JA; Wigmore, SJ.

In: Transplantation, Vol. 88, No. 3, 01.08.2009, p. 308-316.

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Devey, L ; Mohr, Elodie ; Bellamy, C ; Simpson, K ; Henderson, N ; Harrison, EM ; Ross, JA ; Wigmore, SJ. / c-Jun Terminal Kinase-2 Gene Deleted Mice Overexpress Hemeoxygenase-1 and Are Protected From Hepatic Ischemia Reperfusion Injury. In: Transplantation. 2009 ; Vol. 88, No. 3. pp. 308-316.

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@article{950b15fe92a84b8282801df41caa2995,
title = "c-Jun Terminal Kinase-2 Gene Deleted Mice Overexpress Hemeoxygenase-1 and Are Protected From Hepatic Ischemia Reperfusion Injury",
abstract = "Background. Targeted deletion of c-jun amino terminal kinase-2 (jnk-2) upregulates the activator protein-1 transcription factor system. We hypothesized that this would lead to induction of hemeoxygenase-1 (HO-1) and confer protection from hepatic ischemia reperfusion injury. Methods. Wild-type and jnk-2-/- animals were subjected to hepatic ischemia reperfusion insults in two models: a total hepatic ischemia model involving timed Pringle maneuver, and a partial hepatic ischemia model involving selective occlusion of the portal pedicle supplying the left hepatic lobe. Optimal durations of injury were calibrated for each model. After 24hr, animals were killed, and blood and tissues were collected for alanine aminotransferase, histologic injury scoring, and other analyses. Before total or partial hepatic ischemia reperfusion insults, some animals were subject to HO-I inhibition with chromium mesoporphyrin IX or Kupffer cell depletion with liposomal clodronate. Bone marrow-derived monocytes were grown from hemopoietic progenitors taken from wild-type and jnk-2-/- mice before stimulation with lipopolysaccharide and measurement of tumour necrosis factor-a production. Results. Jnk-2-/- animals were protected from hepatic ischemia reperfusion injury. HO-I expression and activity was elevated in jnk-2-/- animals (2.2-fold; P=0.006). Most HO-I was expressed in Kupffer cells. Inhibition of HO-I in jnk-2-/- animals led to the loss of protection from ischemia. Depletion of Kupffer cells using liposomal clodronate led to loss of hepatic HO-1 expression and much more severe injury in wild-type and jnk-2-/- animals. In vitro studies of cultured macrophages demonstrated reduced tumour necrosis factor-a secretion after lipopolysacharride stimulus, an effect lost after HO-1 inhibition.",
keywords = "Ischemia reperfusion injury, c-Jun NH2 terminal kinase-2, Hemeoxygenase-1",
author = "L Devey and Elodie Mohr and C Bellamy and K Simpson and N Henderson and EM Harrison and JA Ross and SJ Wigmore",
year = "2009",
month = aug,
day = "1",
doi = "10.1097/TP.0b013e3181ae3067",
language = "English",
volume = "88",
pages = "308--316",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

RIS

TY - JOUR

T1 - c-Jun Terminal Kinase-2 Gene Deleted Mice Overexpress Hemeoxygenase-1 and Are Protected From Hepatic Ischemia Reperfusion Injury

AU - Devey, L

AU - Mohr, Elodie

AU - Bellamy, C

AU - Simpson, K

AU - Henderson, N

AU - Harrison, EM

AU - Ross, JA

AU - Wigmore, SJ

PY - 2009/8/1

Y1 - 2009/8/1

N2 - Background. Targeted deletion of c-jun amino terminal kinase-2 (jnk-2) upregulates the activator protein-1 transcription factor system. We hypothesized that this would lead to induction of hemeoxygenase-1 (HO-1) and confer protection from hepatic ischemia reperfusion injury. Methods. Wild-type and jnk-2-/- animals were subjected to hepatic ischemia reperfusion insults in two models: a total hepatic ischemia model involving timed Pringle maneuver, and a partial hepatic ischemia model involving selective occlusion of the portal pedicle supplying the left hepatic lobe. Optimal durations of injury were calibrated for each model. After 24hr, animals were killed, and blood and tissues were collected for alanine aminotransferase, histologic injury scoring, and other analyses. Before total or partial hepatic ischemia reperfusion insults, some animals were subject to HO-I inhibition with chromium mesoporphyrin IX or Kupffer cell depletion with liposomal clodronate. Bone marrow-derived monocytes were grown from hemopoietic progenitors taken from wild-type and jnk-2-/- mice before stimulation with lipopolysaccharide and measurement of tumour necrosis factor-a production. Results. Jnk-2-/- animals were protected from hepatic ischemia reperfusion injury. HO-I expression and activity was elevated in jnk-2-/- animals (2.2-fold; P=0.006). Most HO-I was expressed in Kupffer cells. Inhibition of HO-I in jnk-2-/- animals led to the loss of protection from ischemia. Depletion of Kupffer cells using liposomal clodronate led to loss of hepatic HO-1 expression and much more severe injury in wild-type and jnk-2-/- animals. In vitro studies of cultured macrophages demonstrated reduced tumour necrosis factor-a secretion after lipopolysacharride stimulus, an effect lost after HO-1 inhibition.

AB - Background. Targeted deletion of c-jun amino terminal kinase-2 (jnk-2) upregulates the activator protein-1 transcription factor system. We hypothesized that this would lead to induction of hemeoxygenase-1 (HO-1) and confer protection from hepatic ischemia reperfusion injury. Methods. Wild-type and jnk-2-/- animals were subjected to hepatic ischemia reperfusion insults in two models: a total hepatic ischemia model involving timed Pringle maneuver, and a partial hepatic ischemia model involving selective occlusion of the portal pedicle supplying the left hepatic lobe. Optimal durations of injury were calibrated for each model. After 24hr, animals were killed, and blood and tissues were collected for alanine aminotransferase, histologic injury scoring, and other analyses. Before total or partial hepatic ischemia reperfusion insults, some animals were subject to HO-I inhibition with chromium mesoporphyrin IX or Kupffer cell depletion with liposomal clodronate. Bone marrow-derived monocytes were grown from hemopoietic progenitors taken from wild-type and jnk-2-/- mice before stimulation with lipopolysaccharide and measurement of tumour necrosis factor-a production. Results. Jnk-2-/- animals were protected from hepatic ischemia reperfusion injury. HO-I expression and activity was elevated in jnk-2-/- animals (2.2-fold; P=0.006). Most HO-I was expressed in Kupffer cells. Inhibition of HO-I in jnk-2-/- animals led to the loss of protection from ischemia. Depletion of Kupffer cells using liposomal clodronate led to loss of hepatic HO-1 expression and much more severe injury in wild-type and jnk-2-/- animals. In vitro studies of cultured macrophages demonstrated reduced tumour necrosis factor-a secretion after lipopolysacharride stimulus, an effect lost after HO-1 inhibition.

KW - Ischemia reperfusion injury

KW - c-Jun NH2 terminal kinase-2

KW - Hemeoxygenase-1

U2 - 10.1097/TP.0b013e3181ae3067

DO - 10.1097/TP.0b013e3181ae3067

M3 - Article

C2 - 19667931

VL - 88

SP - 308

EP - 316

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 3

ER -