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

Choi, Minsu; Chaudhari, Harmesh N.; Ji, Young Rae; Ryoo, Zae Young; Kim, Sang Woo; Yun, Jong Won

doi:10.1007/s11010-015-2468-1

Cited by 5 publications

(5 citation statements)

References 64 publications

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“…Also, a higher concentration of 10 −6 M E 2 reduced both prohibitin and ERα36 protein expression levels and their association in ht-UtLM cells. The difference in the responses to E 2 observed in our study compared to that reported [ 22 ] may due to the unique cell types or concentrations of E 2 used. The presence of ERα36 in mitochondria and its association with the mitochondrial protein prohibitin suggests that ERα36 may mediate critical roles in maintaining mitochondrial structure and function.…”

Section: Discussioncontrasting

confidence: 88%

“…It is reported that prohibitin 2 binds to the ligand binding domain of ERα66 and represses its transcriptional activity [ 16 ]. It has been shown that E 2 stimulates prohibitin expression in white adipose tissue and in the liver of rats [ 22 ]. In a cell culture model (3T3-L1 and C9 cells), transcription and protein levels of prohibitin were also dose-dependently increased by E 2 treatment, further supporting in vivo data that prohibitin expression may be regulated by estrogens and intracellular steroid hormone signaling pathways [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that E 2 stimulates prohibitin expression in white adipose tissue and in the liver of rats [ 22 ]. In a cell culture model (3T3-L1 and C9 cells), transcription and protein levels of prohibitin were also dose-dependently increased by E 2 treatment, further supporting in vivo data that prohibitin expression may be regulated by estrogens and intracellular steroid hormone signaling pathways [ 22 ]. We observed that 10 −8 M E 2 increased prohibitin protein expression and its association with ERα36, but reduced ERα36 levels in ht-UtLM cells.…”

Section: Discussionmentioning

confidence: 99%

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ERα36, a variant of estrogen receptor α, is predominantly localized in mitochondria of human uterine smooth muscle and leiomyoma cells

Yan

Castro

et al. 2017

PLoS ONE

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ERα36 is a naturally occurring, membrane-associated, isoform of estrogen receptor α. The expression of ERα36 is due to alternative splicing and different promoter usage. ERα36 is a dominant-negative effector of ERα66-mediated transactivational activities and has the potential to trigger membrane-initiated mitogenic, nongenomic, estrogen signaling; however, the subcellular localization of ERα36 remains controversial. To determine the cellular localization of ERα36 in estrogen-responsive human uterine smooth muscle (ht-UtSMC) and leiomyoma (fibroid; ht-UtLM) cells, we conducted systematic confocal microscopy and subcellular fractionation analysis using ERα36 antibodies. With Image J colocalizaton analysis plugin, confocal images were analyzed to obtain a Pearson’s Correlation Coefficient (PCC) to quantify signal colocalization of ERα36 with mitochondrial, endoplasmic reticulum, and cytoskeletal components in both cell lines. When cells were double-stained with an ERα36 antibody and a mitochondrial-specific dye, MitoTracker, the PCC for the two channel signals were both greater than 0.75, indicating strong correlation between ERα36 and mitochondrial signals in the two cell lines. A blocking peptide competition assay confirmed that the mitochondria-associated ERα36 signal detected by confocal analysis was specific for ERα36. In contrast, confocal images double-stained with an ERα36 antibody and endoplasmic reticulum or cytoskeletal markers, had PCCs that were all less than 0.4, indicating no or very weak signal correlation. Fractionation studies showed that ERα36 existed predominantly in membrane fractions, with minimal or undetected amounts in the cytosol, nuclear, chromatin, and cytoskeletal fractions. With isolated mitochondrial preparations, we confirmed that a known mitochondrial protein, prohibitin, was present in mitochondria, and by co-immunoprecipitation analysis that ERα36 was associated with prohibitin in ht-UtLM cells. The distinctive colocalization pattern of ERα36 with mitochondria in ht-UtSMC and ht-UtLM cells, and the association of ERα36 with a mitochondrial-specific protein suggest that ERα36 is localized primarily in mitochondria and may play a pivotal role in non-genomic signaling and mitochondrial functions.

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Section: Discussioncontrasting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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ERα36, a variant of estrogen receptor α, is predominantly localized in mitochondria of human uterine smooth muscle and leiomyoma cells

Yan

Castro

et al. 2017

PLoS ONE

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“…al has demonstrated that prohibitin is an estrogen-regulated gene in vitro and vivo , and its expression is induced by estrogen in the uterus 14. Similar result has been observed in white adipose tissue and liver, and the estrogen-elevated prohibitin may mediated by estrogen receptor 15. These results suggest that prohibtin involves in estrogen signaling.…”

Section: Introductionmentioning

confidence: 61%

Estrogen Enhances Endometrial Cancer Cells Proliferation by Upregulation of Prohibitin

Yang¹,

Chen²,

Liang³

et al. 2019

J. Cancer

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Estrogen plays an essential role in type I endometrial cancer cell proliferation. Despite great progresses in the etiology has been obtained in the past, however, the molecular mechanisms remain to be fully clarified. Prohibitin has been demonstrated involvement in multiple cancers' development. If it also contributes to estrogen-driven endometrial cancer proliferation is not clear. IHC assay result display that prohibitin overexpressed in endometrial cancer tissue and associated with the poor prognosis; Western blot assay detect that upregulated prohibitin expression with dose- and time-dependent manners. The cellular growth was monitored with SRB assay which demonstrate that knockdown prohibitin attenuated estrogen-induced proliferation. Ubiquitination assay finds estrogen increased prohibitin level through stabilizing prohibitin protein via inhibition of ubiquitination, while estrogen-induced protein expression was mediated by estrogen receptor. Our findings provide a new insight on the mechanism of estrogen-induced proliferation, implying the possibility of using prohibitin as a potential therapeutic target for the treatment of endometrial cancer.

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“…Of note, Mito-Ob mice started to gain weight during puberty, indicating a relationship between gonadal sex steroids and the observed phenotypes. Emerging evidence from other laboratories also supported a role of PHB in modulating sex steroid actions in a variety of cells and tissues, as well as PHB as a downstream target of sex steroids [ 15 – 17 ]. Specifically, the effect of sex steroids on adipocytes, the site of PHB overexpression in Mito-Ob mice, may contribute to the sex-dimorphic metabolic characteristics described.…”

Section: Introductionmentioning

confidence: 99%

Gonadectomy in Mito-Ob mice revealed a sex-dimorphic relationship between prohibitin and sex steroids in adipose tissue biology and glucose homeostasis

Ande

Mishra

2018

Biol Sex Differ

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BackgroundRecently, we have developed a novel transgenic mouse model by overexpressing prohibitin (PHB) in adipocytes, which developed obesity due to upregulation of mitochondrial biogenesis in adipocytes, hence named “Mito-Ob.” Interestingly, only male Mito-Ob mice developed obesity-related impaired glucose homeostasis and insulin sensitivity, whereas female Mito-Ob mice did not. The observed sex differences in metabolic dysregulation suggest a potential involvement of sex steroids. Thus, the main aim of this study is to investigate the role of sex steroids on the overall phenotype of Mito-Ob mice through gonadectomy, as well as direct effect of sex steroids on adipocytes from Mito-Ob mice in vitro.MethodsMito-Ob mice and wild-type CD-1 mice were gonadectomized at 12 weeks of age. Age- and sex-matched sham-operated mice were used as controls. Body weight, white adipose tissue, glucose tolerance, and insulin sensitivity were analyzed 3 months post-surgery. Differentiation of adipocytes isolated from female and male Mito-Ob mice were studied with and without sex steroids.ResultsGonadectomy significantly reduced body weight in Mito-Ob mice compared with sham-operated mice, whereas the opposite trend was observed in wild-type mice. These changes occurred independent of food intake. A corresponding decrease in adipose tissue weight was found in gonadectomized Mito-Ob mice, but depot-specific differences were observed in male and female. Gonadectomy improved glucose tolerance in male wild-type and Mito-Ob mice, but the effect was more pronounced in wild-type mice. Gonadectomy did not alter insulin sensitivity in male Mito-Ob mice, but it was improved in male wild-type mice. In primary cell cultures, testosterone inhibited adipocyte differentiation to a lesser extent in male Mito-Ob preadipocytes compared with the wild-type mice. On the other hand, preadipocytes from female wild-type mice showed better differentiation potential than those from female Mito-Ob mice in the presence of 17β-estradiol.ConclusionsPHB requires sex steroids for the development of obese phenotype in Mito-Ob mice, which differentially affect glucose homeostasis and insulin sensitivity in male and female. It appears that PHB plays sex- and adipose depot-specific roles and involves additional factors. In vitro studies suggested that PHB differently influenced adipocyte differentiation in the presence and absence of sex steroids. Overall, this study along with available information in the literature indicated that a multifaceted relationship exists between PHB and sex steroids, which may work in a cell/tissue type- and sex-specific manner.

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

Cited by 5 publications

References 64 publications

ERα36, a variant of estrogen receptor α, is predominantly localized in mitochondria of human uterine smooth muscle and leiomyoma cells

ERα36, a variant of estrogen receptor α, is predominantly localized in mitochondria of human uterine smooth muscle and leiomyoma cells

Estrogen Enhances Endometrial Cancer Cells Proliferation by Upregulation of Prohibitin

Gonadectomy in Mito-Ob mice revealed a sex-dimorphic relationship between prohibitin and sex steroids in adipose tissue biology and glucose homeostasis

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