scholarly journals Effects of Vitamin B12 Deficiency on Amyloid-β Toxicity in Caenorhabditis elegans

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 962
Author(s):  
Arif Andra ◽  
Shoko Tanigawa ◽  
Tomohiro Bito ◽  
Atsushi Ishihara ◽  
Fumio Watanabe ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Growth Medium ◽  
Vitamin B12 Deficiency ◽  
Amyloid Β ◽  
Aβ Peptides ◽  
C Elegans ◽  
Aβ Aggregation ◽  
B12 Deficiency ◽  
The Relationship ◽  
Aβ Production

High homocysteine (Hcy) levels, mainly caused by vitamin B12 deficiency, have been reported to induce amyloid-β (Aβ) formation and tau hyperphosphorylation in mouse models of Alzheimer’s disease. However, the relationship between B12 deficiency and Aβ aggregation is poorly understood, as is the associated mechanism. In the current study, we used the transgenic C. elegans strain GMC101, which expresses human Aβ1–42 peptides in muscle cells, to investigate the effects of B12 deficiency on Aβ aggregation–associated paralysis. C. elegans GMC101 was grown on nematode growth medium with or without B12 supplementation or with 2-O-α-D-glucopyranosyl-L-ascorbic acid (AsA-2G) supplementation. The worms were age-synchronized by hypochlorite bleaching and incubated at 20 °C. After the worms reached the young adult stage, the temperature was increased to 25 °C to induce Aβ production. Worms lacking B12 supplementation exhibited paralysis faster and more severely than those that received it. Furthermore, supplementing B12-deficient growth medium with AsA-2G rescued the paralysis phenotype. However, AsA-2G had no effect on the aggregation of Aβ peptides. Our results indicated that B12 supplementation lowered Hcy levels and alleviated Aβ toxicity, suggesting that oxidative stress caused by elevated Hcy levels is an important factor in Aβ toxicity.

The relationship between the cobalt nutrition of ewes and the vitamin B12 status of ewes and their lambs

1987 ◽  
Vol 38 (6) ◽  
pp. 1071 ◽  
Author(s):  
MF Quirk ◽  
BW Norton
Keyword(s):  
Vitamin B12 ◽  
Milk Production ◽  
Acid Concentration ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Lactation Performance ◽  
Lower Productivity ◽  
Cotton South ◽  
B12 Deficiency ◽  
The Relationship

An experiment was undertaken at Mt Cotton, south-east Queensland, to investigate the relationship between the cobalt nutrition of ewes and the occurrence of vitamin B12 deficiency in ewes and their lambs. Ewes received either no supplementary cobalt (C), 0.03 mg cobalt day-1 (LC), 0.06 mg cobalt day-1 (HC) or a cobalt bullet and grinder (CB). LC and HC ewes received their supplement as a weekly drench. Supplementation commenced prior to joining, and ewes subsequently grazed pangola grass pastures containing between 0.05 and 0.11 mg kg-1 cobalt.Cobalt supplementation of ewes increased their liveweight, reproductive and lactation performance. The milk production of ewes was influenced by the level of supplementation, with C, LC, HC and CB ewes producing 31.1, 41.5, 47.7 and 50.31. of milk respectively during the first 4 weeks of lactation. The lower productivity of C ewes was associated with concentrations of vitamin B12 in serum of less than 200 pg ml-1 and with the presence of detectable concentrations of methylmalonic acid (>80 8moles l-1) and formiminoglutamic acid (>30 8moles l-1) in their urine.The growth of lambs was influenced by the cobalt nutrition of their dams; the mean liveweight gain from birth to weaning (14 weeks of age) for lambs from C, LC, HC and CB ewes was 95, 158, 194 and 231 g day-1. Vitamin B12 deficiency was evident in lambs reared by C ewes from 4 weeks of age, but lambs from LC and HC ewes did not become deficient until 8 and 12 weeks of age respectively. Lambs from CB ewes remained free of signs of deficiency prior to weaning. Urinary formiminoglutamic acid concentration was a more reliable indicator of vitamin B12 status in young lambs than urinary methylmalonic acid concentration. The concentrations of vitamin B12 in the serum of lambs were low in all groups (< 150 pg ml-1) and were generally unaffected by the cobalt nutrition of their dams.A dietary cobalt intake of about 0.15 mg day-1 appeared to be necessary for optimal milk production from ewes. However, this level of dietary cobalt was inadequate for provision of sufficient quantities of maternal vitamin B12 to meet the requirements of lambs in the later stages of lactation.

scholarly journals Improved testing for vitamin B12 deficiency: correcting MMA for eGFR reduces the number of patients classified as vitamin B12 deficient

2018 ◽  
Vol 55 (6) ◽  
pp. 685-692 ◽  
Author(s):  
Saskia LM van Loon ◽  
Anna M Wilbik ◽  
Uzay Kaymak ◽  
Edwin R van den Heuvel ◽  
Volkher Scharnhorst ◽  
...  
Keyword(s):  
Data Mining ◽  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
The Elderly ◽  
Vitamin B ◽  
Data Mining Approach ◽  
Number Of Patients ◽  
B12 Deficiency ◽  
The Relationship

Background Methylmalonic acid (MMA) can detect functional vitamin B12 deficiencies as it accumulates early when intracellular deficits arise. However, impaired clearance of MMA from blood due to decreased glomerular filtration rate (eGFR) also results in elevated plasma MMA concentrations. Alternative to clinical trials, a data mining approach was chosen to quantify and compensate for the effect of decreased eGFR on MMA concentration. Methods Comprehensive data on patient’s vitamin B12, eGFR and MMA concentrations were collected ( n = 2906). The relationship between vitamin B12, renal function (eGFR) and MMA was modelled using weighted multiple linear regression. The obtained model was used to estimate the influence of decreased eGFR on MMA. Clinical impact was examined by comparing the number of patients labelled vitamin B12 deficient with and without adjustment in MMA. Results Adjusting measured MMA concentrations for eGFR in the group of patients with low-normal vitamin B12 concentrations (90–300 pmol/L) showed that the use of unadjusted MMA concentrations overestimates vitamin B12 deficiency by 40%. Conclusions Through a data mining approach, the influence of eGFR on the relation between MMA and vitamin B12 can be quantified and used to correct the measured MMA concentration for decreased eGFR. Especially in the elderly, eGFR-based correction of MMA may prevent over-diagnosis of vitamin B12 deficiency and corresponding treatment.

scholarly journals Parkinson’s Disease and Homocysteine: A Community-Based Study in a Folate and Vitamin B12 Deficient Population

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Zhang Wei ◽  
Wang Tiandong ◽  
Li Yang ◽  
Meng Huaxing ◽  
Min Guowen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Vitamin B12 ◽  
Vitamin B12 Deficiency ◽  
Community Based ◽  
Current Smoking ◽  
Blood Samples ◽  
B12 Deficiency ◽  
Folate And Vitamin B12 ◽  
The Relationship

Background. Homocysteine (Hcy) levels were higher in patients with Parkinson’s disease (PD). This could be partially explained by levodopa treatment. Whether untreated PD patients have higher Hcy levels is contradictory.Methods.A community-based study was conducted using a two-stage approach for subjects ≥ 55 years to find PD patients in 3 towns of Lüliang City. Blood samples were collected. Serum Hcy, folate, and vitamin B12 concentrations were measured. For each untreated PD patient, 5 controls were selected matched with age and sex to evaluate the relationship between Hcy levels and PD.Results. Of 6338 eligible residents, 72.7% participated in the study. 31 PD cases were identified. The crude prevalence of PD for people ≥ 55 years was 0.67%. Blood samples were collected from 1845 subjects, including 17 untreated PD patients. There was no difference for concentrations of serum Hcy, folate, and vitamin B12 between cases and controls (P>0.05). In univariate and multivariate analysis, there was significant inverse relation between PD and current smoking (P<0.05). No other factor was significant statistically.Conclusions. The prevalence of PD was comparable to earlier studies in China. Hyperhomocysteinemia was not a risk factor of PD, as well as folate and vitamin B12 deficiency.

scholarly journals Metabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Emma Watson ◽  
Viridiana Olin-Sandoval ◽  
Michael J Hoy ◽  
Chi-Hua Li ◽  
Timo Louisse ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Metabolic Network ◽  
Genetic Interaction ◽  
Vitamin B12 Deficiency ◽  
Selective Advantage ◽  
C Elegans ◽  
In The Wild ◽  
B12 Deficiency ◽  
Mapping Gene ◽  
Network Rewiring

Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditis elegans. Using genetic interaction mapping, gene co-expression analysis, pathway intermediate quantification and carbon tracing, we uncover a vitamin B12-independent propionate breakdown shunt that is transcriptionally activated on vitamin B12 deficient diets, or under genetic conditions mimicking the human diseases propionic- and methylmalonic acidemia, in which the canonical B12-dependent propionate breakdown pathway is blocked. Our study presents the first example of transcriptional vitamin-directed metabolic network rewiring to promote survival under vitamin deficiency. The ability to reroute propionate breakdown according to B12 availability may provide C. elegans with metabolic plasticity and thus a selective advantage on different diets in the wild.

scholarly journals Low Serum Vitamin B12 Levels Are Associated with Adverse Lipid Profiles in Apparently Healthy Young Saudi Women

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2395
Author(s):  
Sara Al-Musharaf ◽  
Ghadeer S. Aljuraiban ◽  
Syed Danish Hussain ◽  
Abdullah M. Alnaami ◽  
Ponnusamy Saravanan ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Lipid Profile ◽  
Serum Vitamin ◽  
Vitamin B12 Deficiency ◽  
Lipid Profiles ◽  
Saudi Women ◽  
B12 Deficiency ◽  
The Relationship ◽  
Low Serum ◽  
Apparently Healthy

An abnormal lipid profile is an independent risk factor for cardiovascular diseases. The relationship between vitamin B12 deficiency and lipid profile is inconclusive, with most studies conducted in unhealthy populations. In this study, we aimed to assess the relationship between serum vitamin B12 levels and lipid profiles in a cross-sectional study that included 341 apparently healthy Saudi women, aged 19–30 years, from different colleges at King Saud University, Saudi Arabia. Sociodemographic, anthropometric, biochemical, and lifestyle data were collected, including diet and physical activity. Serum vitamin B12 deficiency was defined as serum B12 level of <148 pmol/L. The prevalence of vitamin B12 deficiency was approximately 0.6%. Using multivariable linear regression models, serum vitamin B12 levels were found to be inversely associated with total cholesterol (B = −0.26; p < 0.001), low-density lipoprotein cholesterol levels (B = −0.30; p < 0.001), and triglyceride (B = −0.16; p < 0.01) after adjusting for potential confounders, while obesity indices of body mass index, central obesity, and fat percentage showed no association. Therefore, we conclude that low serum vitamin B12 levels are independently associated with abnormal lipid profiles in healthy young Saudi women. Further interventional studies are needed to determine whether improving serum vitamin B12 levels in a healthy population can improve lipid profiles.

scholarly journals Lysosomal activity regulatesCaenorhabditis elegansmitochondrial dynamics through vitamin B12 metabolism

2020 ◽  
Vol 117 (33) ◽  
pp. 19970-19981 ◽  
Author(s):  
Wei Wei ◽  
Gary Ruvkun
Keyword(s):  
Vitamin B12 ◽  
Mitochondrial Biogenesis ◽  
Energy Demand ◽  
Mitochondrial Fission ◽  
Vitamin B12 Deficiency ◽  
Periodic Pattern ◽  
C Elegans ◽  
Lysosomal Dysfunction ◽  
Methionine Restriction ◽  
B12 Deficiency

Mitochondrial fission and fusion are highly regulated by energy demand and physiological conditions to control the production, activity, and movement of these organelles. Mitochondria are arrayed in a periodic pattern inCaenorhabditis elegansmuscle, but this pattern is disrupted by mutations in the mitochondrial fission component dynamin DRP-1. Here we show that the dramatically disorganized mitochondria caused by a mitochondrial fission-defective dynamin mutation is strongly suppressed to a more periodic pattern by a second mutation in lysosomal biogenesis or acidification. Vitamin B12 is normally imported from the bacterial diet via lysosomal degradation of B12-binding proteins and transport of vitamin B12 to the mitochondrion and cytoplasm. We show that the lysosomal dysfunction induced by gene inactivations of lysosomal biogenesis or acidification factors causes vitamin B12 deficiency. Growth of theC. elegansdynamin mutant on anEscherichia colistrain with low vitamin B12 also strongly suppressed the mitochondrial fission defect. Of the twoC. elegansenzymes that require B12, gene inactivation of methionine synthase suppressed the mitochondrial fission defect of a dynamin mutation. We show that lysosomal dysfunction induced mitochondrial biogenesis, which is mediated by vitamin B12 deficiency and methionine restriction. S-adenosylmethionine, the methyl donor of many methylation reactions, including histones, is synthesized from methionine by S-adenosylmethionine synthase; inactivation of thesams-1S-adenosylmethionine synthase also suppresses thedrp-1fission defect, suggesting that vitamin B12 regulates mitochondrial biogenesis and then affects mitochondrial fission via chromatin pathways.

scholarly journals Lysosomal activity regulates Caenorhabditis elegans mitochondrial dynamics through vitamin B12 metabolism

2020 ◽  
Author(s):  
Wei Wei ◽  
Gary Ruvkun
Keyword(s):  
Caenorhabditis Elegans ◽  
Vitamin B12 ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Vitamin B12 Deficiency ◽  
Periodic Pattern ◽  
C Elegans ◽  
Lysosomal Dysfunction ◽  
B12 Deficiency

ABSTRACTMitochondrial fission and fusion are highly regulated by energy demand and physiological conditions to control the production, activity, and movement of these organelles. Mitochondria are arrayed in a periodic pattern in Caenorhabditis elegans muscle, but this pattern is disrupted by mutations in the mitochondrial fission component dynamin. Here we show that the dramatically disorganized mitochondria caused by a mitochondrial fission-defective dynamin mutation is strongly suppressed to a more periodic pattern by a second mutation in lysosomal biogenesis or acidification. Vitamin B12 is normally imported from the bacterial diet via lysosomal degradation of B12-binding proteins and transport of vitamin B12 to the mitochondrion and cytoplasm. We show that the lysosomal dysfunction induced by gene inactivations of lysosomal biogenesis or acidification factors causes vitamin B12 deficiency. Growth of the C. elegans dynamin mutant on an E. coli strain with low vitamin B12 also strongly suppressed the mitochondrial fission defect. Of the two C. elegans enzymes that require B12, gene inactivation of methionine synthase suppressed the mitochondrial fission defect of a dynamin mutation. We show that lysosomal dysfunction induced mitochondrial biogenesis which is mediated by vitamin B12 deficiency and methionine restriction. S-adenosylmethionine, the methyl donor of many methylation reactions, including histones, is synthesized from methionine by S-adenosylmethionine synthase; inactivation of the sams-1 S-adenosylmethionine synthase also suppresses the drp-1 fission defect, suggesting that vitamin B12 regulates mitochondrial biogenesis and then affects mitochondrial fission via chromatin pathways.SIGNIFICANCE STATEMENTThe balance of mitochondrial fission and fusion, two aspects of mitochondrial dynamics, is important for mitochondrial function. Here we show that Caenorhabditis elegans lysosomal activity regulates mitochondrial dynamics by affecting mitochondrial fission through interfering the metabolism of a micronutrient, vitamin B12. Vitamin B12 is exclusively obtained from diets in animals including C. elegans and humans, and its uptake is mediated by the lysosome. We show that lysosomal dysfunction causes vitamin B12 deficiency that leads to reduction of methionine and S-adenosylmethionine to in turn increase mitochondrial biogenesis and fission. Our study provides an insight on the interactions between mitochondrial function and micronutrient metabolism.

scholarly journals Dityrosine Crosslinking of Collagen and Amyloid-β Peptides Is Formed by Vitamin B12 Deficiency-Generated Oxidative Stress in Caenorhabditis elegans

2021 ◽  
Vol 22 (23) ◽  
pp. 12959
Author(s):  
Kyohei Koseki ◽  
Aoi Yamamoto ◽  
Keisuke Tanimoto ◽  
Naho Okamoto ◽  
Fei Teng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Vitamin B12 ◽  
Mrna Expression ◽  
Vitamin B12 Deficiency ◽  
Amyloid Β ◽  
Underlying Mechanism ◽  
Amyloid Β Protein ◽  
Collagen Biosynthesis ◽  
B12 Deficiency

(1) Background: Vitamin B12 deficiency in Caenorhabditis elegans results in severe oxidative stress and induces morphological abnormality in mutants due to disordered cuticle collagen biosynthesis. We clarified the underlying mechanism leading to such mutant worms due to vitamin B12 deficiency. (2) Results: The deficient worms exhibited decreased collagen levels of up to approximately 59% compared with the control. Although vitamin B12 deficiency did not affect the mRNA expression of prolyl 4-hydroxylase, which catalyzes the formation of 4-hydroxyproline involved in intercellular collagen biosynthesis, the level of ascorbic acid, a prolyl 4-hydroxylase coenzyme, was markedly decreased. Dityrosine crosslinking is involved in the extracellular maturation of worm collagen. The dityrosine level of collagen significantly increased in the deficient worms compared with the control. However, vitamin B12 deficiency hardly affected the mRNA expression levels of bli-3 and mlt-7, which are encoding crosslinking-related enzymes, suggesting that deficiency-induced oxidative stress leads to dityrosine crosslinking. Moreover, using GMC101 mutant worms that express the full-length human amyloid β, we found that vitamin B12 deficiency did not affect the gene and protein expressions of amyloid β but increased the formation of dityrosine crosslinking in the amyloid β protein. (3) Conclusions: Vitamin B12-deficient wild-type worms showed motility dysfunction due to decreased collagen levels and the formation of highly tyrosine-crosslinked collagen, potentially reducing their flexibility. In GMC101 mutant worms, vitamin B12 deficiency-induced oxidative stress triggers dityrosine-crosslinked amyloid β formation, which might promote its stabilization and toxic oligomerization.

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