• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3319-3323
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• 2012

Objective: The results from the published studies on the association between prohibitin 3' untranslated region C > T gene polymorphism and cancer risk are conflicting. This meta-analysis was performed to evaluate the relationship with cancer susceptibility overall, and to explore whether the T allele or TT genotype could become a predictive marker for cancer risk. Methods: Association studies were identified from the databases of PubMed, Embase, and Cochrane Library as of March 1, 2012, and eligible investigations were synthesized using the meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. Results: Six investigations were identified for the analysis of association between the prohibitin 3' untranslated region C > T gene polymorphism and cancer risk, covering of 1,461 patients with cancer and 1,197 controls. There was a positive association between the T allele and cancer susceptibility (OR=1.20, 95% CI: 1.03-1.39, P=0.02), and CC homozygous might play a protective role (OR=0.80, 95% CI: 0.68-6.11, P=0.95). In the sub-group analysis, prohibitin 3' untranslated region C > T gene polymorphism and cancer risk appeared associated with the risk of breast cancer, but not ovarian cancer. Conclusions: Our results indicate that T allele is a significant genetic molecular marker to predict cancer susceptibility and CC genotype is protective, especially for breast cancer. However, more investigations are required to further clarify the association of the prohibitin 3' untranslated region C > T gene polymorphism with cancer susceptibility.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5113-5117
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• 2012

Prohibitin (PHB) is a chaperone protein which is highly conserved evolutionarily. It shows significant homology with the Drosophila cc gene which is considered important for development and differentiation of Drosophila melanogaster. Investigations have revealed an involvement of PHB in cellular proliferation and development, apoptosis, signal transduction, mitochondrial function and regulation of the estrogen and androgen receptors. Therefore, we conducted the present study to analyze mutations in the highly conserved region in Indian female breast cancer patients. Conventional PCR-SSCP and Automated DNA sequencing were performed with a total of 105 breast cancer samples along with adjacent normal tissue. Of the total, 14.2% (15/105) demonstrated a mutation status of prohibitin observed in our study population. We identified a novel missense mutation (Thr>Ser), a novel deletion of T nucleotide in an intron adjacent to intron-exon boundary and a previously determined missense mutation (Val>Ala). A statistically significant correlation was obtained which suggested that prohibitin may be associated with tumor development and/or progression of at least some proportion of breast cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3803-3807
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• 2012

Prohibitin (PHB), an evolutionarily-conserved protein, has been found to be over-expressed in gastric cancer and be closely related with tumor malignancy. In this study, to investigate the relationship between PHB expression and cell apoptosis in the BGC823 gastric cancer cell line, low and high expression PHB in BGC823 cells was accomplished using RNA interference technology and gene transfer techniques. Cell proliferation, cell cycling, apoptosis, Bax, Bcl-2 and Cyt.c protein expression and the activation of Caspase-3,9 were assessed after 48h. Over-expression of PHB gene in BGC823 cells resulted in slow cell growth, cell arrest in G2 phase, and an increased apoptosis ratio while the opposite was found for PHB under-expressing cells. In PHB over-expressing cells, the expression of Bax gene was increased, the expression of Bcl-2 was decreased, the activation level of Caspase-3, 9 was increased, but the activation level of Caspase-8 demonstrated no change. These results indicate that PHB induced apoptosis through the mitochondrial pathway.

• Korean Journal of Food Science and Technology
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• v.44 no.6
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• pp.653-657
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• 2012

While it is known that sulfur containing amino acids (SCAA) are very important in regulating hepatocyte growth and preventing liver-diseases, the fundamental molecular mechanisms of how they exert their hepatoprotective functions are not well known. Since it is widely understood that the hepatic concentrations of S-adenosylmethionine (SAMe) in chronic liver disease patients are severely decreased, the pathophysiological importance of SAMe and its downstream antioxidant, glutathione should be discussed in order to see a big picture of relationship between SCAA and liver diseases. Chronic SAMe deficient mice have shown spontaneous hepatocellular carcinoma development due to impaired mitochondria functions with low levels of prohibitin1 protein, and through deficiency in many genes which are known to ameliorate genetic instability, such as APEX1 and DUSP1, the functions of which are recovered by SAMe treatment. In this review, current knowledge of the basic concepts of the mechanisms through which SCAAs protect the liver will be discussed in detail. Also, a possible tumor suppressor in livers, prohibitin1, and its functional relationship with SAMe will be discussed.

• Journal of Microbiology and Biotechnology
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• v.32 no.11
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• pp.1447-1453
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• 2022

Prohibitin 1 (Phb1) is a pleiotropic protein, located mainly in the mitochondrial inner membrane and involved in the regulation of cell proliferation and the stabilization of mitochondrial protein. Acetaminophen (APAP) is one of the most commonly used over-the-counter analgesics worldwide. However, at high dose, the accumulation of N-acetyl-p-benzoquinone imine (NAPQI) can lead to APAP-induced hepatotoxicity. In this study, we sought to understand the regulation of mRNA expression in relation to APAP and GSH metabolism by Phb1 in normal mouse AML12 hepatocytes. We used two different Phb1 silencing levels: high-efficiency (HE, >90%) and low-efficiency (LE, 50-60%). In addition, the siRNA-transfected cells were further pretreated with 0.5 mM of Sadenosylmethionine (SAMe) for 24 h before treatment with APAP at different doses (1-2 mM) for 24 h. The expression of APAP metabolism-related and antioxidant genes such as Cyp2e1 and Ugt1a1 were increased during SAMe pretreatment. Moreover, SAMe increased intracellular GSH concentration and it was maintained after APAP treatment. To sum up, Phb1 silencing and APAP treatment impaired the metabolism of APAP in hepatocytes, and SAMe exerted a protective effect against hepatotoxicity by upregulating antioxidant genes.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.11
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• pp.1729-1737
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• 2018

Objective: The aim of the current study is to investigate the relationship between prohibitin (PHB), capping actin protein of muscle Z-line beta subunit (CAPZB), and tektin-2 (TEKT2) and sperm motility in Murrah buffalo. Methods: We collected the high-motility and low-motility semen samples, testis, ovary, muscle, kidney, liver, brain and pituitary from Murrah buffalo, and analysed the expression of PHB, CAPZB, and TEKT2 in mRNA (message RNA) and protein level. Results: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) result showed that the expression of PHB was higher and CAPZB, TEKT2 were specifically expressed in testis as compared to the other 6 tissues, and that in testis, the expression of TEKT2 was higher than that of CAPZB and PHB. Immunohistochemistry test revealed that all three genes were located on the convoluted seminiferous tubule and enriched in spermatogenic cells. Both qRT-PCR and Western Blot results showed that the expression levels of PHB, CAPZB, and TEKT2 were significantly lower in the low-motility semen group compared to the high-motility semen group (p<0.05). Conclusion: The expression levels of PHB, CAPZB, and TEKT2 in Murrah buffalo sperm have a high positive correlation with sperm motility. And the three genes may be potential molecular markers for the decline of buffalo sperm motility.

• Journal of Microbiology and Biotechnology
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• v.21 no.12
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• pp.1211-1227
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• 2011

C57BL/6J mice have been widely used as a diet-induced obesity model because they trigger common features of the human metabolic syndrome. In the present study, C57BL/6J male mice were fed either a high-fat diet (HFD) or normal diet (ND) during a 24-week period, and then the age-dependent liver proteome of mice in two groups was analyzed using 2-DE combined with MALDI-TOF-MS. Among identified proteins, up-regulated proteins were subdivided to early (during the first 4 weeks) and late (20~24 weeks) markers that played a role in diet-induced obesity development. Important early markers included ketohexokinase and prohibitin, and late markers included the 75 kDa glucose-regulated protein, citrate synthase, and selenium-binding liver protein. Of these, the 75 kDa glucosere-gulated protein has already been linked to obesity; however, prohibitin protein involved in obesity was identified for the first time in this study. In order to validate the proteomic results and gain insight into metabolic changes between the two groups, we further confirmed the expression pattern of some proteins of interest by Western blot analysis. Combined results of proteomic analysis with Western blot analysis revealed that antioxidant enzymes were progressively decreased, whereas cytoskeletal proteins were time-dependently increased in HFD mice.

• Toxicological Research
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• v.17
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• pp.59-69
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• 2001

Arsenic exposure is associated with several human diseases, including cancers, atherosclerosis, hypertension, and cerebrovascular diseases. In cultured cells, arsenite, an inorganic arsenic com-pound, was demonstrated to interfere with many physiological functions, such as enhancement of oxidative stress, delay of cell cycle progression, and induction of structural and numerical changes of chromosomes. The objective of this study is to investigate the effects of arsenic exposure on gene expression profiles by colorimetric cDNA microarray technique. HFW (normal human diploid skin fibroblasts), CL3 (human lung adenocarcinoma cell line), and HaCaT (immortalized human keratinocyte cell line) were treated with 5 $\mu\textrm{M}$ or 10 $\mu\textrm{M}$ sodium arsenite for 6 or 16 h, respectively. By a dual-color detection system, the expression profile of arsenite-treated cultures was compared to that of control cultures. Several genes expressed differentially were identified on the microarray membranes. For example, MDM2, SWI/SNF, ubiquitin specific protease 4, MAP3K11, RecQ protein-like 5, and Ribosomal protein Ll0a were consistently induced in all three cell types by arsenite, whereas prohibitin, cyclin D1, nucleolar protein 1, PCNA, Nm23, and immediate early protein (ETR101) were apparently inhibited. The present results suggest that arsenite insults altered the expression of several genes participating in cellular responses to DNA damage, stress, transcription, and cell cycle arrest.

• BMB Reports
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• v.40 no.2
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• pp.212-217
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• 2007

The chicken oviduct is a dynamic organ that produces secretory proteins such as ovalbumin during the laying period. In this study, we identified oviduct-specific proteins in hens during the egg-laying period by proteomic analysis. Proteins extracted from the magnum of hens of different ages (5, 35, and 65 weeks) were analyzed by two-dimensional gel electrophoresis to compare the intensity of proteins among samples. Approximately 300 spots were detected on each gel. Based on the comparison of image gels, we found that the intensity of eight spots in 35-week magnums was increased at least by 2-fold compared with the others. Five of the eight spots were identified as calumenin, acidic ribosomal phosphoproteins (ARP), prohibitin, heart fatty acid-binding protein, and anterior gradient-2 (AGR-2). In particular, ARP and AGR-2 were highly expressed in 35- week magnums compared with 5- and 65-week magnums. In addition, the level of these proteins was consistent with their RNA levels. Expression of AGR-2 mRNA was detected in the mature magnum, whereas no signal was observed in premature tissue. Among various tissues, expression of AGR-2 mRNA was highest in the magnum, high in the isthmus, and five fold lower in muscle. It was undetectable in the liver and in other tissues (heart and kidney). However, the mRNA levels of other proteins were ubiquitous among tissues. In transcriptional activity of AGR-2, a 3.0 kb fragment of promoter region containing potential estrogen receptor binding sites had enhanced its activity strongly. In conclusion, these results suggest that AGR-2 has functional regulatory roles in the chicken oviduct during the egglaying period.