Insights into S-adenosyl-l-methionine (SAM)-dependent methyltransferase related diseases and genetic polymorphisms

Li, Jiaojiao; Sun, Chunxiao; Cai, Wenwen; Li, Jing; Rosen, Barry P.; Chen, Jian

doi:10.1016/j.mrrev.2021.108396

Cited by 22 publications

(14 citation statements)

References 185 publications

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“…DNA methylation typically refers to the transfer of a methyl group from S‐adenosylmethionine (SAM) to DNA through the action of DNA methyltransferases (DNMTs) (Li, Sun, et al., 2021 ), which generally happens on the 5‐position carbon of cytosines in CpG dinucleotides (Soto‐Palma et al., 2022 ). CpG islands (CGIs) are regions with CpG‐rich DNA sequences, usually located within or near gene promotors (Bird, 1986 ; Bird et al., 1985 ; Saxonov et al., 2006 ), and methylation of CGIS promotors could silence gene expression (Robertson & Wolffe, 2000 ).…”

Section: How Do Hallmarks Of Aging Participate In the Pathogenesis Of...mentioning

confidence: 99%

Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging

Wang,

Yuan,

Wang

et al. 2024

Aging Cell

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Osteoarthritis (OA), a chronic degenerative joint disease, is highly prevalent among the aging population, and often leads to joint pain, disability, and a diminished quality of life. Although considerable research has been conducted, the precise molecular mechanisms propelling OA pathogenesis continue to be elusive, thereby impeding the development of effective therapeutics. Notably, recent studies have revealed subchondral bone lesions precede cartilage degeneration in the early stage of OA. This development is marked by escalated osteoclast‐mediated bone resorption, subsequent imbalances in bone metabolism, accelerated bone turnover, and a decrease in bone volume, thereby contributing significantly to the pathological changes. While the role of aging hallmarks in OA has been extensively elucidated from the perspective of chondrocytes, their connection with osteoclasts is not yet fully understood. There is compelling evidence to suggest that age‐related abnormalities such as epigenetic alterations, proteostasis network disruption, cellular senescence, and mitochondrial dysfunction, can stimulate osteoclast activity. This review intends to systematically discuss how aging hallmarks contribute to OA pathogenesis, placing particular emphasis on the age‐induced shifts in osteoclast activity. It also aims to stimulate future studies probing into the pathological mechanisms and therapeutic approaches targeting osteoclasts in OA during aging.

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Section: How Do Hallmarks Of Aging Participate In the Pathogenesis Of...mentioning

confidence: 99%

Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging

Wang,

Yuan,

Wang

et al. 2024

Aging Cell

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“…It is a substrate for many enzyme‐catalyzed reactions and provides methyl groups in many biological methylations. [ 1 ] In the medical field, SAM can be used to treat arthritis, heavy depression, liver diseases, and low sperm activity in infertile patience. [ 2 ] SAM is formed from L‐Methionine (L‐Met) and ATP as direct precursors catalyzed by S‐adenosylmethionine synthetase controlled by SAM2 gene in organisms.…”

Section: Introductionmentioning

confidence: 99%

Enhanced synthesis of S‐adenosyl‐L‐methionine through combinatorial metabolic engineering and Bayesian optimization in Saccharomyces cerevisiae

Xiao,

Shi,

Huang

et al. 2024

Biotechnology Journal

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S‐Adenosyl‐L‐methionine (SAM) is a substrate for many enzyme‐catalyzed reactions and provides methyl groups in numerous biological methylations, and thus has vast applications in the agriculture and medical field. Saccharomyces cerevisiae has been engineered as a platform with significant potential for producing SAM, but the current production has room for improvement. Thus, a method that consists of a series of metabolic engineering strategies was established in this study. These strategies included enhancing SAM synthesis, increasing ATP supply, down‐regulating SAM metabolism, and down‐regulating competing pathway. After combinatorial metabolic engineering, Bayesian optimization was conducted on the obtained strain C262P6S to optimize the fermentation medium. A final yield of 2972.8 mg·L−1 at 36 h with 29.7% of the L‐Met conversion rate in the shake flask was achieved, which was 26.3 times higher than that of its parent strain and the highest reported production in the shake flask to date. This paper establishes a feasible foundation for the construction of SAM‐producing strains using metabolic engineering strategies and demonstrates the effectiveness of Bayesian optimization in optimizing fermentation medium to enhance the generation of SAM.

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“…Hcy accumulation can cause SAH accumulation, which in turn leads to inhibition of methylation reactions and a decrease in DNA methylation levels [ 18 ]. Therefore, the current view suggests that Hcy forms connections with DNA methylation through SAM and SAH in the methionine cycle, occupying an important junction between carbon metabolism and epigenetic modifications [ 19 ]. Multiple studies have demonstrated a correlation between elevated Hcy levels and reduced DNA methylation levels.…”

Section: Introductionmentioning

confidence: 99%

Tangshen formula improves diabetic nephropathy in STZ-induced diabetes rats fed with hyper-methionine by regulating the methylation status of kidney

Jiang,

Deng,

Liu

et al. 2024

Clin Epigenet

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Background The objective of this study was to examine and analyze differential methylation profiles in order to investigate the influence of hyper-methioninemia (HM) on the development of diabetic nephropathy (DN). Male Wistar rats, aged eight weeks and weighing 250–300 g, were randomly assigned into four groups: a control group (Healthy, n = 8), streptozocin-induced rats (STZ group, n = 8), HM + STZ group (n = 8), and the Tangshen Formula (TSF) treatment group (TSF group, n = 8). Blood glucose levels and other metabolic indicators were monitored before treatment and at four-week intervals until 12 weeks. Total DNA was extracted from the aforementioned groups, and DNA methylation landscapes were analyzed via reduced representative bisulfite sequencing. Results Both the STZ group and HM + STZ group exhibited increased blood glucose levels and urinary albumin/creatinine ratios in comparison with the control group. Notably, the HM + STZ group exhibited a markedly elevated urinary albumin/creatinine ratio (411.90 ± 88.86 mg/g) compared to the STZ group (238.41 ± 62.52 mg/g). TSF-treated rats demonstrated substantial reductions in both blood glucose levels and urinary albumin/creatinine ratios in comparison with the HM + STZ group. In-depth analysis of DNA methylation profiles revealed 797 genes with potential therapeutic effects related to TSF, among which approximately 2.3% had been previously reported as homologous genes. Conclusion While HM exacerbates DN through altered methylation patterns at specific CpG sites, TSF holds promise as a viable treatment for DN by restoring abnormal methylation levels. The identification of specific genes provides valuable insights into the underlying mechanisms of DN pathogenesis and offers potential therapeutic targets for further investigation.

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Insights into S-adenosyl-l-methionine (SAM)-dependent methyltransferase related diseases and genetic polymorphisms

Cited by 22 publications

References 185 publications

Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging

Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging

Enhanced synthesis of S‐adenosyl‐L‐methionine through combinatorial metabolic engineering and Bayesian optimization in Saccharomyces cerevisiae

Tangshen formula improves diabetic nephropathy in STZ-induced diabetes rats fed with hyper-methionine by regulating the methylation status of kidney

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