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Hepatic ischemia/reperfusion upregulates the susceptibility of hepatocytes to confer the induction of inducible nitric oxide synthase gene expression.
Shock 2006; 26(2):162-8S

Abstract

During hepatic ischemia/reperfusion (I/R), proinflammatory cytokines such as tumor necrosis factor alpha and interleukin (IL) 1beta stimulate the induction of inducible nitric oxide synthase (iNOS) in hepatocytes, followed by massive production of nitric oxide. We hypothesized that I/R upregulated the susceptibility of hepatocytes to confer the induction of iNOS gene expression. This study was designed to investigate whether cell susceptibility occurs in response to I/R and to delineate the mechanisms underlying the susceptibility. Hepatocytes were isolated from rats with hepatic I/R or sham, cultured, and treated with IL-1beta. The iNOS induction and its signal including inhibitor kappaB (IkappaB) kinase/nuclear factor kappaB (NF-kappaB) and Akt/type 1 interleukin 1 receptor (IL-1R1) were analyzed. Hepatocytes isolated from rats with I/R markedly increased the production of nitric oxide when stimulated by IL-1beta as compared with sham control. Ischemia/R also increased the levels of iNOS protein and its messenger RNA. Furthermore, I/R enhanced the activation of transcription factor NF-kappaB and the transactivation of iNOS promoter. However, I/R had no effects on the degradation of IkappaB and the nuclear translocation of p65 subunit of NF-kappaB. In contrast, I/R increased the phosphorylation of Akt and the upregulation of IL-1R1 induction, which is essential signal for the transcriptional activation of iNOS in addition to IkappaB kinase/NF-kappaB. These results demonstrate that I/R may augment hepatocyte susceptibility for the induction of iNOS gene expression through the enhancement of IL-1R1.

Authors+Show Affiliations

The Department of Surgery, Kansai Medical University, Osaka 570-8506, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16878024

Citation

Yanagida, Hidesuke, et al. "Hepatic Ischemia/reperfusion Upregulates the Susceptibility of Hepatocytes to Confer the Induction of Inducible Nitric Oxide Synthase Gene Expression." Shock (Augusta, Ga.), vol. 26, no. 2, 2006, pp. 162-8.
Yanagida H, Kaibori M, Yoshida H, et al. Hepatic ischemia/reperfusion upregulates the susceptibility of hepatocytes to confer the induction of inducible nitric oxide synthase gene expression. Shock. 2006;26(2):162-8.
Yanagida, H., Kaibori, M., Yoshida, H., Habara, K., Yamada, M., Kamiyama, Y., & Okumura, T. (2006). Hepatic ischemia/reperfusion upregulates the susceptibility of hepatocytes to confer the induction of inducible nitric oxide synthase gene expression. Shock (Augusta, Ga.), 26(2), pp. 162-8.
Yanagida H, et al. Hepatic Ischemia/reperfusion Upregulates the Susceptibility of Hepatocytes to Confer the Induction of Inducible Nitric Oxide Synthase Gene Expression. Shock. 2006;26(2):162-8. PubMed PMID: 16878024.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatic ischemia/reperfusion upregulates the susceptibility of hepatocytes to confer the induction of inducible nitric oxide synthase gene expression. AU - Yanagida,Hidesuke, AU - Kaibori,Masaki, AU - Yoshida,Hideyuki, AU - Habara,Kozo, AU - Yamada,Masanori, AU - Kamiyama,Yasuo, AU - Okumura,Tadayoshi, PY - 2006/8/1/pubmed PY - 2006/10/25/medline PY - 2006/8/1/entrez SP - 162 EP - 8 JF - Shock (Augusta, Ga.) JO - Shock VL - 26 IS - 2 N2 - During hepatic ischemia/reperfusion (I/R), proinflammatory cytokines such as tumor necrosis factor alpha and interleukin (IL) 1beta stimulate the induction of inducible nitric oxide synthase (iNOS) in hepatocytes, followed by massive production of nitric oxide. We hypothesized that I/R upregulated the susceptibility of hepatocytes to confer the induction of iNOS gene expression. This study was designed to investigate whether cell susceptibility occurs in response to I/R and to delineate the mechanisms underlying the susceptibility. Hepatocytes were isolated from rats with hepatic I/R or sham, cultured, and treated with IL-1beta. The iNOS induction and its signal including inhibitor kappaB (IkappaB) kinase/nuclear factor kappaB (NF-kappaB) and Akt/type 1 interleukin 1 receptor (IL-1R1) were analyzed. Hepatocytes isolated from rats with I/R markedly increased the production of nitric oxide when stimulated by IL-1beta as compared with sham control. Ischemia/R also increased the levels of iNOS protein and its messenger RNA. Furthermore, I/R enhanced the activation of transcription factor NF-kappaB and the transactivation of iNOS promoter. However, I/R had no effects on the degradation of IkappaB and the nuclear translocation of p65 subunit of NF-kappaB. In contrast, I/R increased the phosphorylation of Akt and the upregulation of IL-1R1 induction, which is essential signal for the transcriptional activation of iNOS in addition to IkappaB kinase/NF-kappaB. These results demonstrate that I/R may augment hepatocyte susceptibility for the induction of iNOS gene expression through the enhancement of IL-1R1. SN - 1073-2322 UR - https://www.unboundmedicine.com/medline/citation/16878024/Hepatic_ischemia/reperfusion_upregulates_the_susceptibility_of_hepatocytes_to_confer_the_induction_of_inducible_nitric_oxide_synthase_gene_expression_ L2 - http://dx.doi.org/10.1097/01.shk.0000223130.87382.73 DB - PRIME DP - Unbound Medicine ER -