S-adenosyl-homocysteine-hydrolase (AHCY) plays an important role in the methionine cycle regulating cellular methylation levels. AHCY has been reported to influence proliferation and differentiation processes in different cell types, e.g. in cancer cells and mouse embryonic stem cells. In the development of adipose tissue, both the proliferation and differentiation of adipocyte progenitor cells (APCs) are important processes, which in the context of obesity are often dysregulated. To assess whether AHCY might also be involved in cell proliferation and differentiation of APCs, we investigated the effect of reduced AHCY activity on human and mouse APCs . We show that the inhibition of AHCY using adenosine dialdehyde (AdOx) and the knockdown of AHCY using gene-specific siRNAs reduced APC proliferation and number. Inhibition of AHCY further reduced APC differentiation into mature adipocytes and the expression of adipogenic differentiation markers. Global DNA methylation profiling in human APCs revealed that inhibition of AHCY is associated with alterations in CpG methylation levels of genes involved in fat cell differentiation and pathways related to cellular growth. Our findings suggest that AHCY is necessary for the maintenance of APC proliferation and differentiation and inhibition of AHCY alters DNA methylation processes leading to a dysregulation of the expression of genes involved in the regulation of these processes.
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http://dx.doi.org/10.1080/21623945.2023.2290218 | DOI Listing |
bioRxiv
November 2024
Georgetown University, Lombardi Comprehensive Cancer Center, 3970 Reservoir Rd NW Washington D.C. 20007, United States of America.
Glioblastoma (GBM) is a highly aggressive primary malignant adult brain tumor that inevitably recurs with a fatal prognosis. This is due in part to metabolic reprogramming that allows tumors to evade treatment. We therefore must uncover the pathways mediating these adaptations to develop novel and effective treatments.
View Article and Find Full Text PDFJ Dermatol Sci
December 2024
Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, China. Electronic address:
Biomolecules
July 2024
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Adipocyte
December 2024
Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany.
S-adenosyl-homocysteine-hydrolase (AHCY) plays an important role in the methionine cycle regulating cellular methylation levels. AHCY has been reported to influence proliferation and differentiation processes in different cell types, e.g.
View Article and Find Full Text PDFBiol Reprod
March 2024
College of Life Science, Northeast Agricultural University, Harbin, China.
Adenosylhomocysteinase (AHCY), a key enzyme in the methionine cycle, is essential for the development of embryos and the maintenance of mouse embryonic stem cells (mESCs). However, the precise underlying mechanism of Ahcy in regulating pluripotency remains unclear. As the only enzyme that can hydrolyze S-adenosylhomocysteine in mammals, AHCY plays a critical role in the metabolic homeostasis, epigenetic remodeling, and transcriptional regulation.
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