Format

Send to

Choose Destination
Biochem Biophys Res Commun. 2018 Jan 1;495(1):976-981. doi: 10.1016/j.bbrc.2017.11.098. Epub 2017 Nov 21.

Cereblon deficiency confers resistance against polymicrobial sepsis by the activation of AMP activated protein kinase and heme-oxygenase-1.

Author information

1
Nano-Bio Resources Center, Department of Cosmetic Sciences, Sookmyung Women's University, Seoul, Republic of Korea.
2
Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
3
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
4
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: cspark@amc.seoul.kr.
5
Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea. Electronic address: kjlee@amc.seoul.kr.

Abstract

Cereblon (CRBN) has a pleiotropic role in important cellular processes and is a potential therapeutic target in several diseases, including mental retardation, cancer, and metabolic disorders. The role of CRBN in polymicrobial sepsis induced by cecal ligation and puncture (CLP) was investigated using CRBN-deficient (KO) mice. Survival following CLP was significantly higher in KO mice compared to wild-type (WT) controls (50% vs 0% at day 6 after CLP). The improved survival of KO mice was accompanied by reduced peripheral blood bacterial load and lung injury. Serum tumor necrosis factor (TNF)-α and high mobility group box 1 (HMGB1) concentrations were significantly lower in KO mice than in WT mice. Peritoneal macrophages from KO mice with CLP-induced septic mouse had higher levels of activation of AMPK and heme oxygenase-1 (HO-1). Forced expression of CRBN in macrophage of KO mice suppressed activation of 5' adenosine monophosphate-activated protein kinase (AMPK) and HO-1 and augmented expression of TNF-α and HMGB1 as inhibition of AMPK by compound C. These studies demonstrate the contribution of CRBN expression to the pathogenesis of CLP-induced sepsis and peritoneal macrophage responses and suggest a novel therapeutic modality for polymicrobial sepsis.

KEYWORDS:

AMPK; CLP; Cereblon; HMGB1; Heme oxygenase-1

PMID:
29170136
DOI:
10.1016/j.bbrc.2017.11.098
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center