scholarly journals Matrix metalloproteinases-2, -3 and tissue inhibitors of metalloproteinases-1, -2 in placentas from preterm pregnancies and their association with one-carbon metabolites

Reproduction ◽  
2013 ◽  
Vol 145 (4) ◽  
pp. 401-410 ◽  
Author(s):  
Deepali Sundrani ◽  
Preeti Chavan-Gautam ◽  
Hemlata Pisal ◽  
Savita Mehendale ◽  
Sadhana Joshi

Maternal nutrition is an important determinant of one-carbon metabolism and defects in the one-carbon metabolism may lead to poor obstetric outcomes. This study was designed to test the hypothesis that altered intake/metabolism of micronutrients (folic acid and vitamin B12) and docosahexaenoic acid (DHA) contributes to increased homocysteine and oxidative stress leading to altered levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in women delivering preterm. We have earlier reported increased vitamin B12, homocysteine, and oxidative stress along with reduced placental DHA in women delivering preterm. In this study, we further examine the placental levels of MMP2, MMP3, TIMP1, and TIMP2 in 75 women delivering at term and 73 women delivering preterm. Placental levels of MMPs and TIMPs were determined by ELISA. Placental MMP2 and MMP3 levels were higher (P<0.01) in women delivering preterm as compared with term. There was no difference in the placental TIMP1 and TIMP2 levels in women delivering preterm and at term. Further placental MMP2 and MMP3 levels were higher (P<0.01) in women with preterm labor as compared with those in labor at term, suggesting that MMPs may favor degradation of extracellular matrix in the placenta during preterm labor. Our study for the first time suggests a crucial role of micronutrients and MMPs in preterm birth. Future studies need to examine if epigenetic modifications through the one-carbon cycle contribute to increased levels of MMPs leading to preterm deliveries.

2004 ◽  
Vol 4 ◽  
pp. 736-745 ◽  
Author(s):  
Ebere C. Anyanwu ◽  
Mohammed Morad ◽  
Andrew W. Campbell

This paper evaluates the possible reasons for consistent vitamin B12deficiency in chronic toxigenic mold exposures and the synergistic relationships with the possible mycotoxic effects on one-carbon metabolism that lead to the manifestations of clinical neuropathological symptomology. Vitamins are first defined in general and the nutritional sources of vitamin B12are evaluated in particular. Since patients with chronic exposures to toxigenic molds manifest vitamin B12deficiencies, the role of mycotoxins in vitamin B12metabolism is assessed, and since vitamin B12plays important biochemical roles in one-carbon metabolism, the synergistic effects with mycotoxins on humans are reviewed. An outline of the proposed mechanism by which mycotoxins disrupt or interfere with the normal functions of vitamin B12on one-carbon metabolism is proposed. The overall functions of vitamin B12as a source of coenzymes, in intracellular recycling of methionine, in methionine synthase reaction, in the prevention of chromosome breakage, in methylation, and in maintaining a one-carbon metabolic balance are reviewed. Signs, symptoms, and clinical neurological indications of vitamin B12deficiency are also cited. By implication and derivation, it is likely that the interruption of the structure and function of vitamin B12would in turn interfere with the one-carbon metabolism leading to the neurological manifestations. This review is an attempt to formulate a basis for an ongoing research investigation on the subject.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Danielle N. Coleman ◽  
Abdulrahman S. Alharthi ◽  
Yusheng Liang ◽  
Matheus Gomes Lopes ◽  
Vincenzo Lopreiato ◽  
...  

AbstractDairy cattle undergo dramatic metabolic, endocrine, physiologic and immune changes during the peripartal period largely due to combined increases in energy requirements for fetal growth and development, milk production, and decreased dry matter intake. The negative nutrient balance that develops results in body fat mobilization, subsequently leading to triacylglycerol (TAG) accumulation in the liver along with reductions in liver function, immune dysfunction and a state of inflammation and oxidative stress. Mobilization of muscle and gluconeogenesis are also enhanced, while intake of vitamins and minerals is decreased, contributing to metabolic and immune dysfunction and oxidative stress. Enhancing post-ruminal supply of methyl donors is one approach that may improve immunometabolism and production synergistically in peripartal cows. At the cellular level, methyl donors (e.g. methionine, choline, betaine and folic acid) interact through one-carbon metabolism to modulate metabolism, immune responses and epigenetic events. By modulating those pathways, methyl donors may help increase the export of very low-density lipoproteins to reduce liver TAG and contribute to antioxidant synthesis to alleviate oxidative stress. Thus, altering one-carbon metabolism through methyl donor supplementation is a viable option to modulate immunometabolism during the peripartal period. This review explores available data on the regulation of one-carbon metabolism pathways in dairy cows in the context of enzyme regulation, cellular sensors and signaling mechanisms that might respond to increased dietary supply of specific methyl donors. Effects of methyl donors beyond the one-carbon metabolism pathways, including production performance, immune cell function, mechanistic target or rapamycin signaling, and fatty acid oxidation will also be highlighted. Furthermore, the effects of body condition and feeding system (total mixed ration vs. pasture) on one-carbon metabolism pathways are explored. Potential effects of methyl donor supply during the pepartum period on dairy calf growth and development also are discussed. Lastly, practical nutritional recommendations related to methyl donor metabolism during the peripartal period are presented. Nutritional management during the peripartal period is a fertile area of research, hence, underscoring the importance for developing a systems understanding of the potential immunometabolic role that dietary methyl donors play during this period to promote health and performance.


2012 ◽  
Vol 302 (1) ◽  
pp. E61-E67 ◽  
Author(s):  
Simon G. Lamarre ◽  
Anne M. Molloy ◽  
Stacey N. Reinke ◽  
Brian D. Sykes ◽  
Margaret E. Brosnan ◽  
...  

Formate can differentiate between hyperhomocysteinemia due to impaired remethylation and impaired transsulfuration. Am J Physiol Endocrinol Metab 301: E000–E000, 2011. First published September 20, 2011; 10.1152/ajpendo.00345.2011.—We carried out a1H-NMR metabolomic analysis of sera from vitamin B12-deficient rats. In addition to the expected increases in methylmalonate and homocysteine (Hcy), we observed an approximately sevenfold increase in formate levels, from 64 μM in control rats to 402 μM in vitamin B12-deficient rats. Urinary formate was also elevated. This elevation of formate could be attributed to impaired one-carbon metabolism since formate is assimilated into the one-carbon pool by incorporation into 10-formyl-THF via the enzyme 10-formyl-THF synthase. Both plasma and urinary formate were also increased in folate-deficient rats. Hcy was elevated in both the vitamin B12- and folate-deficient rats. Although plasma Hcy was also elevated, plasma formate was unaffected in vitamin B6-deficient rats (impaired transsulfuration pathway). These results were in accord with a mathematical model of folate metabolism, which predicted that reduction in methionine synthase activity would cause increased formate levels, whereas reduced cystathionine β-synthase activity would not. Our data indicate that formate provides a novel window into cellular folate metabolism, that elevated formate can be a useful indicator of deranged one-carbon metabolism and can be used to discriminate between the hyperhomocysteinemia caused by defects in the remethylation and transsulfuration pathways.


Author(s):  
Per Magne Ueland ◽  
Pål I. Holm ◽  
Steinar Hustad

AbstractBetaine serves as a methyl donor in a reaction converting homocysteine to methionine, catalysed by the enzyme betaine-homocysteine methyltransferase. It has been used for years to lower the concentration of plasma total homocysteine (tHcy) in patients with homocystinuria, and has recently been shown to reduce fasting and in particular post-methionine load (PML) tHcy in healthy subjects.Betaine exists in plasma at concentrations of about 30μmol/L; it varies 10-fold (from 9 to 90μmol/L) between individuals, but the intra-individual variability is small. Major determinants are choline, dimethylglycine and folate in plasma, folic acid intake and gender.Recent studies have demonstrated that plasma betaine is a stronger determinant of PML tHcy than are vitamin BTo conclude, betaine status is a component of an individual's biochemical make-up with ramifications to one-carbon metabolism. Betaine status should be investigated in pathologies related to altered metabolism of homocysteine and folate, including cardiovascular disease, cancer and neural tube defects.


2018 ◽  
Vol 275 (12) ◽  
pp. 3075-3082 ◽  
Author(s):  
Valéria Souza Freitas ◽  
Jean Nunes dos Santos ◽  
Pedro Paulo de Andrade Santos ◽  
Cassiano Francisco Weege Nonaka ◽  
Leão Pereira Pinto ◽  
...  

2018 ◽  
Vol 10 (4) ◽  
pp. 306-311 ◽  
Author(s):  
Jian-feng Zhang ◽  
Gang-liang Wang ◽  
Zhi-jie Zhou ◽  
Xiang-qian Fang ◽  
Shuai Chen ◽  
...  

Apmis ◽  
2001 ◽  
Vol 109 (4) ◽  
pp. 305-315 ◽  
Author(s):  
M. Soderstrom ◽  
H. T. Aro ◽  
M. Ahonen ◽  
N. Johansson ◽  
A. Aho ◽  
...  

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