Patients with mild forms of peroxisomal biogenesis disorders show facial dysmorphism and exhibit dentition problems accompanied by enamel hypoplasia. However, no information is available on the role of peroxisomes in dental and paradontal tissues. Therefore, we studied the distribution of these organelles, their protein composition and the expression of corresponding genes during dental development and in mature decalcified teeth in mice. Perfusion-fixed heads of mice of different developmental stages (E13.5 to adult) were cut in sagittal direction into two halves and embedded in paraffin for serial sectioning and subsequent peroxidase-based immunohistochemistry or double-immunofluorescence preparations. Frozen, unfixed heads of newborn mice were used for cryosectioning and subsequent laser-assisted microdissection of ameloblasts and odontoblasts, RNA isolation and RT-PCR analysis. Our results revealed the presence of peroxisomes already in the bud stage of dental development. An increase in peroxisome abundance was noted during differentiation of ameloblasts and odontoblasts with the highest number of organelles in Tomes' processes of mature ameloblasts. A strong heterogeneity of peroxisomal enzyme content developed within differentiated dental cell types. A drastic down-regulation of catalase in maturing ameloblasts was noted in contrast to high levels of lipid metabolizing enzymes in peroxisomes of these cells. As known from the literature, differentiated ameloblasts are more prone to oxidative damage which could be explained by the low catalase levels inside of this cell type.
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http://dx.doi.org/10.1007/s00418-013-1131-8 | DOI Listing |
PLoS One
December 2024
Institute of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
Human peroxisomal biogenesis disorders of the Zellweger syndrome spectrum affect skeletal development and induce tooth malformations. Whereas several peroxisomal knockout mouse studies elucidated the pathogenesis of skeletal defects, little information is available on how dental pathologies arise in peroxisomal biogenesis disorder patients. To understand the impact of severe peroxisomal dysfunction on early odontogenesis, here we performed morphometric studies on developing molars of new-born Pex11b knockout mice.
View Article and Find Full Text PDFBMJ Open
November 2024
Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Kanagawa, Japan
Introduction: Non-alcoholic fatty liver disease, now known as metabolic dysfunction-associated steatotic liver disease (MASLD), is a phenotype of the metabolic syndrome in the liver and is clearly associated with metabolic abnormalities such as hyperglycaemia and dyslipidaemia. Although the prevalence of MASLD is increasing worldwide, there is currently no consensus on the efficacy and safety of the drugs used to treat MASLD/metabolic dysfunction-associated steatohepatitis (MASH). Pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, was designed to have higher peroxisome proliferator-activated receptor alfa (PPARα) agonist activity and selectivity than existing PPARα agonists, and in development trials, without increasing creatinine levels, lipid parameters and alanine aminotransferase (ALT) were significantly improved.
View Article and Find Full Text PDFNat Commun
October 2024
Department of Biomolecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University (TMDU) (Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Peroxisomes are organelles that are central to lipid metabolism and chemical detoxification. Despite advances in our understanding of peroxisome biogenesis, the mechanisms maintaining peroxisomal membrane proteins remain to be fully elucidated. We show here that mammalian FAF2/UBXD8, a membrane-associated cofactor of p97/VCP, maintains peroxisomal homeostasis by modulating the turnover of peroxisomal membrane proteins such as PMP70.
View Article and Find Full Text PDFAdv Exp Med Biol
September 2024
Department of Diabetes, Metabolism and Endocrinology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Brown and beige adipocytes produce heat from substrates such as fatty acids and glucose. Such heat productions occur in response to various stimuli and are called adaptive non-shivering thermogenesis. This review introduces mechanisms known to regulate brown and beige adipocyte thermogenesis.
View Article and Find Full Text PDFNutr Metab (Lond)
September 2024
Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Background: Breast cancer is the most diagnosed cancer in women. Its pathogenesis includes several pathways in cancer proliferation, apoptosis, and metastasis. Some clinical data have indicated the association between coffee consumption and decreased cancer risk.
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