Vitamin B6 Deficiency, Genome Instability and Cancer

Wu, Xiayu; Lin, Lü

doi:10.7314/apjcp.2012.13.11.5333

Cited by 37 publications

(23 citation statements)

References 75 publications

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“…RIP140 participates in adipocyte fat accumulation and lipogenesis and in the maintenance of white adipocyte phenotype [33,34]. Otherwise, PLP is a cofactor required for the optimal activity of both mitochondrial and cytoplasmic isoenzymes of serine hydroxymethyltransferase (SHMT1) and (SHMT2) [35,36]. These enzymes are essential in folate-mediated one-carbon metabolism, which is compartmentalised in the mitochondria and cytoplasm and is known to have an important role in DNA methylation, synthesis and repair [36,37].…”

Section: Discussionmentioning

confidence: 99%

Metabolomics uncovers the role of adipose tissue PDXK in adipogenesis and systemic insulin sensitivity

et al. 2016

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Aims/hypothesis We aimed to investigate the potential mechanisms involved in the compromised adipogenesis of visceral (VAT) vs subcutaneous adipose tissue (SAT) using comparative metabolomics. Based on the differentially identified metabolites, we focused on the relationship between the active form of vitamin B 6 (pyridoxal 5-phosphate [PLP]), known to be generated through pyridoxal kinase (PDXK), and adipogenesis. Methods Non-targeted metabolomics analyses were performed in paired VAT and SAT (n = 14, discovery cohort). PDXK gene expression was evaluated in two validation cohorts of paired SAT and VAT samples in relation to obesity status and insulin sensitivity, and mechanistically after weight loss in vivo and in 3T3-L1 cells in vitro.Results Comparative metabolomics showed that PLP was significantly decreased in VAT vs SAT. Concordantly, PDXK mRNA levels were significantly decreased in VAT vs SAT, specifically in adipocytes. The decrease was specially marked in obese individuals. PDXK mRNA levels showed a strong association with adipogenic, lipid-droplet-related and lipogenic genes. At a functional level, systemic insulin sensitivity positively associated with PDXK expression, and surgically-induced weight loss (improving insulin sensitivity) led to increased SAT PDXK mRNA levels in parallel with adipogenic genes. In human pre-adipocytes, PDXK mRNA levels increased during adipocyte differentiation and after administration of peroxisome proliferator-activated receptor-γ agonists, and decreased under inflammatory stimuli. Mechanistic studies in 3T3-L1 cells showed that PLP administration resulted in increased adipogenic mRNA markers during early adipogenesis, whereas the PLP antagonist 4-deoxypyridoxine exerted opposite effects. Conclusions/interpretation Overall, these results support the notion that in situ production of PLP is required for physiological adipogenesis.

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Section: Discussionmentioning

confidence: 99%

Metabolomics uncovers the role of adipose tissue PDXK in adipogenesis and systemic insulin sensitivity

et al. 2016

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“…Vitamin B6 has been implicated in the regulation of immune responses that are associated with a wide range of diseases, including inflammation [11] and various cancers [1, 12, 13]. Previous studies suggested that vitamin B6 deficiency could impair immune responses.…”

Section: Introductionmentioning

confidence: 99%

Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations

Bian

Shen

Zhang

et al. 2017

Journal of Immunology Research

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The immune system is critical in preventing infection and cancer, and malnutrition can weaken different aspects of the immune system to undermine immunity. Previous studies suggested that vitamin B6 deficiency could decrease serum antibody production with concomitant increase in IL4 expression. However, evidence on whether vitamin B6 deficiency would impair immune cell differentiation, cytokines secretion, and signal molecule expression involved in JAK/STAT signaling pathway to regulate immune response remains largely unknown. The aim of this study is to investigate the effects of vitamin B6 deficiency on the immune system through analysis of T lymphocyte differentiation, IL-2, IL-4, and INF-γ secretion, and SOCS-1 and T-bet gene transcription. We generated a vitamin B6-deficient mouse model via vitamin B6-depletion diet. The results showed that vitamin B6 deficiency retards growth, inhibits lymphocyte proliferation, and interferes with its differentiation. After ConA stimulation, vitamin B6 deficiency led to decrease in IL-2 and increase in IL-4 but had no influence on IFN-γ. Real-time PCR analysis showed that vitamin B6 deficiency downregulated T-bet and upregulated SOCS-1 transcription. This study suggested that vitamin B6 deficiency influenced the immunity in organisms. Meanwhile, the appropriate supplement of vitamin B6 could benefit immunity of the organism.

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“…The cytosolic serine hydroxymethyl transferase 1 (SHMT1) catalyzes the reversible conversion of serine and tetrahydrofolate to glycine and 5, 10-methylene tetrahydrofolate [14,15] and is a critical enzyme in one carbon (methyl) metabolism [14][15][16][17]. One carbon transfer is a key component in amino acid and nucleotide synthesis as well as methylation of proteins, DNA and RNA [18,19] and, thus, participating in the regulation of cell function, proliferation and growth [18,20].…”

Section: Introductionmentioning

confidence: 99%

Role of Cytosolic Serine Hydroxymethyl Transferase 1 (SHMT1) in Phosphate-Induced Vascular Smooth Muscle Cell Calcification

Boehme

Schelski

Makridakis

et al. 2018

Kidney Blood Press Res

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Background/Aims: Hyperphosphatemia promotes medial vascular calcification, at least partly, by induction of osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). The complex signaling pathways regulating this process are still incompletely understood. The present study investigated the role of cytosolic serine hydroxymethyl transferase 1 (SHMT1) in phosphate-induced vascular calcification. Methods: Endogenous expression of SHMT1 was suppressed by silencing in primary human aortic smooth muscle cells (HAoSMCs) followed by treatment without and with phosphate or antioxidants. Results: In HAoSMCs, SHMT1 mRNA expression was up-regulated by phosphate. Silencing of SHMT1 alone was sufficient to induce osteo-/chondrogenic transdifferentiation of HAoSMCs, as shown by increased tissue-nonspecific alkaline phosphatase (ALPL) activity and osteogenic markers MSX2, CBFA1 and ALPL mRNA expression. Furthermore, phosphate-induced ALPL mRNA expression and activity as well as calcification were augmented in SHMT1 silenced HAoSMCs as compared to negative control siRNA transfected HAoSMCs. Silencing of SHMT1 decreased total antioxidant capacity and up-regulated NADH/NADPH oxidase system components NOX4 and CYBA mRNA expression in HAoSMCs, effects paralleled by increased mRNA expression of matrix metalloproteinase MMP2 as well as BAX/BCL2 ratio. More importantly, additional treatment with antioxidants TEMPOL or TIRON blunted the increased osteogenic markers mRNA expression in SHMT1 silenced HAoSMCs. Conclusion: Silencing of SHMT1 promotes osteo-/chondrogenic signaling in VSMCs, at least in part, by inducing cellular oxidative stress. It thus aggravates phosphate-induced calcification of VSMCs. The present findings support a regulatory role of SHMT1 in vascular calcification during conditions of hyperphosphatemia such as chronic kidney disease.

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Vitamin B6 Deficiency, Genome Instability and Cancer

Cited by 37 publications

References 75 publications

Metabolomics uncovers the role of adipose tissue PDXK in adipogenesis and systemic insulin sensitivity

Metabolomics uncovers the role of adipose tissue PDXK in adipogenesis and systemic insulin sensitivity

Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations

Role of Cytosolic Serine Hydroxymethyl Transferase 1 (SHMT1) in Phosphate-Induced Vascular Smooth Muscle Cell Calcification

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