Prohibitin-1 deficiency promotes inflammation and increases sensitivity to liver injury

Prohibitin (PHB) is a ubiquitously expressed and highly conserved protein that participates in diverse cellular processes, and its functions are linked to a variety of diseases. In the present study, to explore transcriptional activation and signaling pathways involved in PHB regulation in response to sex hormone treatment, we investigated the effects of estrogen (17-β-estradiol, E2) on regulation of PHB in several metabolic tissues from male and female rats. Elevated expression of PHB was prominent in white adipose tissue (WAT) and the liver, and E2 stimulated PHB expression in both ND and HFD-fed rats. To further confirm the expression of PHB which was increased in WAT and the liver, we analyzed PHB expression levels in 3T3-L1 and C9 cells after the treatment of E2. Transcription and protein levels of PHB were dose-dependently increased by E2 treatment in both cell types, supporting our in vivo data. To further evaluate the possible role of E2 in elevation of PHB via estrogen receptors (ER), the potent ER inhibitor fulvestrant was treated to 3T3-L1 and C9 cells. Fulvestrant markedly suppressed both transcription and protein levels of PHB, suggesting that PHB expression in both tissues may be regulated through ERs. GeneMANIA, a predictive web interface, was used to show that Phb is regulated via the intracellular steroid hormone receptor signaling pathway, suggesting a role for ERs in expression of Phb as well as other metabolically important genes. Based on these results, we expect that targeting PHB would be a useful therapeutic approach for treatment of obesity.

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“…PHB has been linked to a variety of diseases such as cancer [5], obesity [6], and inflammation [7,8].…”

Section: Introductionmentioning

confidence: 99%

Effect of estrogen on expression of prohibitin in white adipose tissue and liver of diet-induced obese rats

Choi

Chaudhari

et al. 2015

Mol Cell Biochem

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“…This requires phosphorylation of PHB at tyrosine-114 and -259 (Y114 and Y259) residues [9], which have been reported earlier in the context of receptor tyrosine kinase signaling [8,34]. PHB has been shown to attenuate colonic inflammation in mice [35], whereas its deficiency promotes inflammation and increases sensitivity to liver injury [36]. …”

mentioning

confidence: 97%

Prohibitin in Adipose and Immune Functions

Ande

Nguyen

Nyomba

et al. 2016

Trends in Endocrinology & Metabolism

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“…[31][32][33] Sánchez-Quiles et al reported that prohibitin-1 deficiency promoted inflammation and increased sensitivity to liver injury induced by MCD diet in mice. 34 In this work, treatment with geraniol enhanced prohibitin expression in livers of MCD rats.…”

Section: Discussionmentioning

confidence: 66%

Treatment with geraniol ameliorates methionine‐choline‐deficient diet‐induced non‐alcoholic steatohepatitis in rats

Fan

Zhou

Gao

2016

J of Gastro and Hepatol

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Prohibitin-1 deficiency promotes inflammation and increases sensitivity to liver injury

Cited by 23 publications

References 50 publications

Effect of estrogen on expression of prohibitin in white adipose tissue and liver of diet-induced obese rats

Effect of estrogen on expression of prohibitin in white adipose tissue and liver of diet-induced obese rats

Prohibitin in Adipose and Immune Functions

Treatment with geraniol ameliorates methionine‐choline‐deficient diet‐induced non‐alcoholic steatohepatitis in rats

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