Molecular and cellular effects of vitamin B12 in brain, myocardium and liver through its role as co-factor of methionine synthase

Guéant, Jean‐Louis; Caillerez-Fofou, Maatem; Battaglia-Hsu, Shyue-Fang; Alberto, Jean-Marc; Freund, Jean–Noël; Dulluc, Isabelle; Adjalla, Charles; Maury, Florence; Merle, Carole; Nicolas, Jean‐Pierre; Namour, Farès; Daval, Jean‐Luc

doi:10.1016/j.biochi.2013.01.020

Cited by 80 publications

(57 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This study revealed a significant difference in methylation profiles in DNA isolated from blood compared to DNA isolated from heart tissues. Further, 22 samples from the heart showed increased methylation in fetuses having DS compared to fetuses having normal karyotypes (19,20). The present paper focuses on the presence of CHD due to genetic polymorphism present in the genes of folate metabolism to their occurrence in DS offspring.…”

Section: Resultsmentioning

confidence: 92%

MTHFR promoter hypermethylation may lead to congenital heart defects in Down syndrome

Asim

Panigrahi

Saiyed

et al. 2017

IRDR

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 92%

MTHFR promoter hypermethylation may lead to congenital heart defects in Down syndrome

Asim

Panigrahi

Saiyed

et al. 2017

IRDR

View full text Add to dashboard Cite

“…In assessing the regulatory parameters that might control PP2A carboxyl methylation in the CNS, there has been a focus on factors that underlie methylation metabolism such as levels of the methyl donor, S‐adenosylmethionine (SAM), the competitive inhibitor, S‐adenosyl homocysteine (SAH), or the methylation cycle intermediate homocysteine. Accordingly, there is considerable evidence that SAM and SAH levels play a substantial role in regulating PP2A 30, 31, 32, 33, 34. Conditions of methylation and one carbon stress have been shown to cause DNA hypomethylation at loci that appear to contribute to the pathogenesis of PD 35, 36, 37.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of protein phosphatase 2A in parkinson disease and dementia with lewy bodies

Park

Lee

Park

et al. 2016

Ann Clin Transl Neurol

View full text Add to dashboard Cite

ObjectiveProtein phosphatase 2A (PP2A) is a heterotrimeric holoenzyme composed of a catalytic C subunit, a structural A subunit, and one of several regulatory B subunits that confer substrate specificity. The assembly and activity of PP2A are regulated by reversible methylation of the C subunit. α‐Synuclein, which aggregates in Parkinson disease (PD) and dementia with Lewy bodies (DLB), is phosphorylated at Ser129, and PP2A containing a B55α subunit is a major phospho‐Ser129 phosphatase. The objective of this study was to investigate PP2A in α‐synucleinopathies.MethodsWe compared the state of PP2A methylation, as well as the expression of its methylating enzyme, leucine carboxyl methyltransferase (LCMT‐1), and demethylating enzyme, protein phosphatase methylesterase (PME‐1), in postmortem brains from PD and DLB cases as well as age‐matched Controls. Immunohistochemical studies and quantitative image analysis were employed.Results LCMT‐1 was significantly reduced in the substantia nigra (SN) and frontal cortex in both PD and DLB. PME‐1, on the other hand, was elevated in the PD SN. In concert with these changes, the ratio of methylated PP2A to demethylated PP2A was markedly decreased in PD and DLB brains in both SN and frontal cortex. No changes in total PP2A or total B55α subunit were detected.InterpretationThese findings support the hypothesis that PP2A dysregulation in α‐synucleinopathies may contribute to the accumulation of hyperphosphorylated α‐synuclein and to the disease process, raising the possibility that pharmacological means to enhance PP2A phosphatase activity may be a useful disease‐modifying therapeutic approach.

show abstract

“…The synthesis of methionine also produces tetrahydrofolic acid, which is essential for a number of folate-dependent reactions [11,15], such as DNA synthesis [16]. The loss of this function is demonstrated in individuals with vitamin B12 deiciency, which explains why cobalamin deiciency often mimics folic acid deiciency.…”

Section: Metabolism Of Vitamin B12mentioning

confidence: 99%

“…Methylmalonyl-CoA mutase catalyzes conversion of methylmalonyl-CoA to succinyl-CoA (Figure 2), an important metabolite in the Krebs cycle [16] and essential factor for the degradation of odd-chain faty acids. In individuals with B12 deiciency, the activity of methylmalonyl-CoA mutase is dam- aged, and as a result, the levels of methylmalonic acid (MMA) in the body increase [11,18].…”

Section: Metabolism Of Vitamin B12mentioning

confidence: 99%

Vitamin B12: Could It Be a Promising Immunotherapy?

Todorova¹,

Ermenlieva²,

Tsankova³

2017

Immunotherapy - Myths, Reality, Ideas, Future

View full text Add to dashboard Cite

Vitamin B12 is a water-soluble vitamin and an important micronutrient with critical role in DNA, protein, and lipid synthesis. It is responsible for one-carbon metabolism and cell division of nervous and hematopoietic cells. Among its various functions, the role as immunomodulator in cellular immunity, especially in elevating the number of CD8+ cells and NK cells, atracts scientiic interest. Many alternative anticancer and anti-inlammatory treatments involve the use of B12 together with other vitamins and nutrients, but still the scientiic information is too obscure and insuicient. Controversial data link tumorigenesis with either increased or decreased B12 blood levels in diferent types of cancer. Dietary intake and additional supplement with the vitamin do not protect against cancer risk, but the dominant opinion is to integrate B12 as part of rational and healthy nutrition to ensure proper function of the immune system. This chapter will review in brief the most important facts for vitamin B12 functions and properties. We will try also to present in concise way the human immune system and the exact role of B12 in immune activity with emphasis on the questionable participation of vitamin B12 in the process of carcinogenesis and its signiicance as anticancer immunotherapy.Keywords: vitamin B12, immunonutrition, immunomodulation, immunotherapy, tumorigenesis, cancer, inlammation IntroductionCancer is the inal outcome of uncontrolled overgrowth of normal cells. Cancer cells remain insensitive to antiproliferative signals and apoptosis. As a result, they replicate, proliferate, and invade ininitely and aggressively. Although the genetic events are thought to be the most important in the process of carcinogenesis, other factors can facilitate abnormal cell development. For many years, inlammation and anti-inlammatory response were widely associated with malignancy [1, 2] and recognized as major elements that trigger carcinogenesis.© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Extended inlammation, especially in chronic infections, predisposes to cancer, but still the mechanism(s) involved is (are) not deinitely known. Usually all inlammatory processes are followed rapidly by anti-inlammatory defense response-excessive production of proinlammatory signals (mediators) and reactive oxygen and nitrogen species. The pro-inlammatory mediators (cytokines, chemokines, and eicosanoids) may stimulate proliferation of both untransformed and tumor cells [2]. The reactive oxygen and nitrogen species lead to oxidative stress and damage of macromolecules, especially DNA to increase the risk of genetic mutations and tumorigenesis [3].A continuously increasing number of microelements, vitamins, and mineral salts are reported to modulate the immune response and counter the inlamm...

show abstract

Molecular and cellular effects of vitamin B12 in brain, myocardium and liver through its role as co-factor of methionine synthase

Cited by 80 publications

References 63 publications

MTHFR promoter hypermethylation may lead to congenital heart defects in Down syndrome

MTHFR promoter hypermethylation may lead to congenital heart defects in Down syndrome

Dysregulation of protein phosphatase 2A in parkinson disease and dementia with lewy bodies

Vitamin B12: Could It Be a Promising Immunotherapy?

Contact Info

Product

Resources

About