Immunohistochemical activity of Prohibitin-2 and Stomatin-Like Protein-2 in patients with ulcerative colitis

Kucuk, Irfan; Tanoğlu, Alpaslan; Öncü, Kemal; Yılmaz, İsmail; Kara, Muammer; Beyazıt, Yavuz; Akyol, Taner; Kaplan, Mustafa; Ozari, Halil Onur; Yazgan, Yusuf

doi:10.5152/tjg.2016.15460

Cited by 5 publications

(7 citation statements)

References 29 publications

(38 reference statements)

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“…PHB2 was shown to govern fatty acid composition in macrophages 62 . In line with the present findings, which showed that overexpressing PHB2 is an effective way to reduce myocardial inflammation and normalize heart performance under endotoxemia conditions, evidence from rodent models of arthritis 63 , spondylarthropathies 64 , ulcerative colitis 65 , and endotoxin-mediated acute lung injury 66 highlighted also the functional importance of PHB2 in neutralizing abnormal inflammatory responses.…”

Section: Discussionsupporting

confidence: 91%

Pgam5-mediated PHB2 dephosphorylation contributes to endotoxemia-induced myocardial dysfunction by inhibiting mitophagy and the mitochondrial unfolded protein response

Cai,

Li,

Zheng

et al. 2023

Int. J. Biol. Sci.

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Numerous mitochondrial abnormalities are reported to result from excessive inflammation during endotoxemia. Prohibitin 2 (PHB2) and phosphoglycerate mutase 5 (Pgam5) have been associated with altered mitochondrial homeostasis in several cardiovascular diseases; however, their role in endotoxemia-related myocardial dysfunction has not been explored. Our experiments were aimed to evaluate the potential contribution of Pgam5 and PHB2 to endotoxemia-induced mitochondrial dysfunction in cardiomyocytes, with a focus on two endogenous protective programs that sustain mitochondrial integrity, namely mitophagy and the mitochondrial unfolded protein response (UPR mt ). We found that PHB2 transgenic mice are resistant to endotoxemia-mediated myocardial depression and mitochondrial damage. Our assays indicated that PHB2 overexpression activates mitophagy and the UPR mt , which maintains mitochondrial metabolism, prevents oxidative stress injury, and enhances cardiomyocyte viability. Molecular analyses further showed that Pgam5 binds to and dephosphorylates PHB2, resulting in cytosolic translocation of mitochondrial PHB2. Silencing of Pgam5 or transfection of a phosphorylated PHB2 mutant in mouse HL-1 cardiomyocytes prevented the loss of mitochondrially-localized PHB2 and activated mitophagy and UPR mt in the presence of LPS. Notably, cardiomyocyte-specific deletion of Pgam5 in vivo attenuated LPS-mediated myocardial dysfunction and preserved cardiomyocyte viability. These findings suggest that Pgam5/PHB2 signaling and mitophagy/UPR mt are potential targets for the treatment of endotoxemia-related cardiac dysfunction.

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Section: Discussionsupporting

confidence: 91%

Pgam5-mediated PHB2 dephosphorylation contributes to endotoxemia-induced myocardial dysfunction by inhibiting mitophagy and the mitochondrial unfolded protein response

Cai,

Li,

Zheng

et al. 2023

Int. J. Biol. Sci.

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“…Studies have reported that SLP-2 is upregulated in a variety of cancer types, including esophageal squamous cell carcinoma ( 26 ), epithelial ovarian cancer ( 27 ) and non-small cell lung cancer, amongst others ( 28 ), and that SLP-2-silencing significantly reduces cancer progression ( 29 ). Notably, SLP-2 acts as a pro-inflammatory factor in patients with colitis and liver cancer ( 30 , 31 ). Thus, STOM may affect the oxidative stress and inflammation of alveolar epithelial cells induced by sepsis.…”

Section: Discussionmentioning

confidence: 99%

Stomatin‑knockdown effectively attenuates sepsis‑induced oxidative stress and inflammation of alveolar epithelial cells by regulating CD36

Wang

2021

Exp Ther Med

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Sepsis-induced acute lung injury is a type of lung disease with a high fatality rate that is characterized by acute inflammation. In the present study, the underlying role and potential mechanism of the stomatin (STOM) protein were investigated in lipopolysaccharide (LPS)-induced oxidative stress and inflammation in a mouse lung epithelial cell line, MLE-12. The expression levels of STOM and CD36 were measured using reverse transcription-quantitative PCR and western blotting. Subsequently, the expression levels of STOM and CD36 in LPS-treated MLE-12 cells were knocked down or overexpressed, respectively, via transfection with a small interfering RNA-STOM or a CD36-overexpression vector. An RNA immunoprecipitation (RIP) assay was used to determine the interaction between STOM and CD36, while Cell Counting Kit-8 assay and ELISA were performed to detect cell viability and oxidative stress, respectively. Moreover, western blotting and ELISA kits were used to detect the expression levels of associated inflammatory factors. The results of the present study demonstrated that STOM expression was upregulated in MLE-12 cells treated with LPS compared with the untreated control group. According to the Search Tool for the Retrieval of Interacting Genes/Proteins database, it was predicted that STOM and CD36 had the ability to interact with each other. The predicted binding between STOM and CD36 was verified using a RIP assay. The results demonstrated that STOM positively regulated the expression of CD36. Moreover, in LPS-treated MLE-12 cells, STOM-knockdown reversed the inhibitory effects of LPS on cell viability, and the promoting effects of LPS on oxidative stress and inflammation. These aforementioned changes were alleviated by the overexpression of CD36. To conclude, the results of the present study revealed that STOM may interact with CD36 to affect the levels of oxidative stress and inflammation in LPS-treated MLE-12 cells.

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“…Increasing levels of prooxidant spermine oxidase in colonic mucosa in parallel to the increasing endoscopic and histopathologic activity of the disease has been observed as well [28] ( Supplementary Table S1). In turn, Küçük et al [104] reported weak positive correlation between endoscopic and histopathologic activity of UC and the immunoreactivity of antioxidant prohibin 2 ( Supplementary Table S3); however, provided scatterplots do not support the notion. Other authors have investigated blood-based markers and reported their significant correlation with the disease endoscopic activity.…”

Section: Markers Of Mucosal Healingmentioning

confidence: 94%

“…Finally, two proteins with antioxidant functionality with differential expression in IBD patients and healthy individuals were reported: elevated serum metallothionein in UC [69] and mucosal prohibin 2, down-regulated in UC [104].…”

Section: Diagnostic Markers In Ucmentioning

confidence: 99%

Oxidative Stress Markers in Inflammatory Bowel Diseases: Systematic Review

et al. 2020

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Precise diagnostic biomarker in inflammatory bowel diseases (IBD) is still missing. We conducted a comprehensive overview of oxidative stress markers (OSMs) as potential diagnostic, differential, progression, and prognostic markers in IBD. A Pubmed, Web of Knowledge, and Scopus search of original articles on OSMs in IBD, published between January 2000 and April 2020, was conducted. Out of 874 articles, 79 eligible studies were identified and used to prepare the interpretative synthesis. Antioxidants followed by lipid peroxidation markers were the most popular and markers of oxidative DNA damage the least popular. There was a disparity in the number of retrieved papers evaluating biomarkers in the adult and pediatric population (n = 6). Of the reviewed OSMs, a promising performance has been reported for serum total antioxidant status as a mucosal healing marker, mucosal 8-OHdG as a progression marker, and for multi-analyte panels of lipid peroxidation products assessed non-invasively in breath as diagnostic and differential markers in the pediatric population. Bilirubin, in turn, was the only validated marker. There is a desperate need for non-invasive biomarkers in IBD which, however, will not be met in the near future by oxidative stress markers as they are promising but mostly at the early research phase of discovery.

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Immunohistochemical activity of Prohibitin-2 and Stomatin-Like Protein-2 in patients with ulcerative colitis

Cited by 5 publications

References 29 publications

Pgam5-mediated PHB2 dephosphorylation contributes to endotoxemia-induced myocardial dysfunction by inhibiting mitophagy and the mitochondrial unfolded protein response

Pgam5-mediated PHB2 dephosphorylation contributes to endotoxemia-induced myocardial dysfunction by inhibiting mitophagy and the mitochondrial unfolded protein response

Stomatin‑knockdown effectively attenuates sepsis‑induced oxidative stress and inflammation of alveolar epithelial cells by regulating CD36

Oxidative Stress Markers in Inflammatory Bowel Diseases: Systematic Review

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