Betaine-rich sugar beet molasses protects from homocysteine-induced reduction of survival in Caenorhabditis elegans
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Homocysteine (Hcy) in humans represents a blood-borne biomarker which predicts the risk of age-related diseases and mortality. Using the nematode Caenorhabditis elegans, we tested whether feeding betaine-rich sugar beet molasses affects the survival under heat stress in the presence of Hcy, in spite of a gene loss in betaine–homocysteine methyltransferase.
Knockdown of the genes relevant for remethylation or transsulfuration of Hcy was achieved by RNA interference (RNAi). Survival assay was conducted under heat stress at 37 °C and Hcy levels were determined by enzyme-linked immunosorbent assay.
Addition of 500 mg/l betaine-rich sugar beet molasses (SBM) prevented the survival reduction that was caused by exposure to Hcy at 37 °C. Although SBM was no longer capable of reducing Hcy levels under RNAi versus homologues for 5, 10-methylenetetrahydrofolate reductase or cystathionine-β-synthase, it still enabled the survival extension by SBM under exposure to Hcy. In contrast, RNAi for the small heat shock protein hsp-16.2 or the foxo transcription factor daf-16 both prevented the extension of survival by betaine-rich molasses in the presence of Hcy.
Our studies demonstrate that betaine-rich SBM is able to prevent survival reduction caused by Hcy in C. elegans in dependence on hsp-16.2 and daf-16 but independent of the remethylation pathway.
KeywordsCaenorhabditis elegans Betaine Homocysteine Heat shock proteins Daf-16
sugar beet molasses
Compliance with ethical standards
Conflict of interest
The authors declare that no conflict of interest exists.
- 1.Boldyrev AA (2009) Molecular mechanisms of homocysteine toxicity. Biochemistry 74(6):589–598Google Scholar
- 2.Haynes WG (2002) Hyperhomocysteinemia, vascular function and atherosclerosis: effects of vitamins. Cardiovasc Drugs Ther 16(5):391–399Google Scholar
- 3.Seshadri S, Beiser A, Selhub J, Jacques PF et al (2002) Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 346(7):476–483Google Scholar
- 5.Barron E, Lara J, White M, Mathers JC (2015) Blood-borne biomarkers of mortality risk: systematic review of cohort studies. PLoS One 10(6):e0127550. https://doi.org/10.1371/journal.pone.0127550.eCollection2015 Google Scholar
- 12.Brenner S (1974) The genetics of Caenorhabditis elegans. Genetics 77(1):71–94Google Scholar
- 15.Timmons L, Court D, Fire A (2001) Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene 263(1–2):103–112Google Scholar
- 16.Gill MS, Olsen A, Sampayo JN, Lithgow GJ (2003) An automated high-throughput assay for survival of the nematode Caenorhabditis elegans. Free Radic Biol Med 35:558–565Google Scholar
- 17.Wierzbicki AS (2007) Homocysteine and cardiovascular disease: a review of the evidence. Diabetes Vasc Dis Res 4(2):143–150Google Scholar
- 18.Parnetti L, Bottiglieri T, Lowenthal D (1997) Role of homocysteine in age-related vascular and non-vascular diseases. Aging 9(4):241–257Google Scholar
- 19.McCully KS (2009) Chemical pathology of homocysteine. IV. Excitotoxicity, oxidative stress, endothelial dysfunction, and inflammation. Ann Clin Lab Sci 39(3):219–232Google Scholar
- 22.Finkelstein JD, Martin JJ (1984) Methionine metabolism in mammals. Distribution of homocysteine between competing pathways. J Biol Chem 259(15):9508–9513Google Scholar
- 23.Gregory JF, DeRatt BN, Rios-Avila L, Ralat M, Stacpoole PW (2016) Vitamin B6 nutritional status and cellular availability of pyridoxal 5′-phosphate govern the function of the transsulfuration pathway’s canonical reactions and hydrogen sulfide production via side reactions. Biochimie 126:21–26. https://doi.org/10.1016/j.biochi.2015.12.020 Google Scholar
- 24.Módis K, Coletta C, Asimakopoulou A, Szczesny B et al (2014) Effect of S-adenosyl-l-methionine (SAM), an allosteric activator of cystathionine-β-synthase (CBS) on colorectal cancer cell proliferation and bioenergetics in vitro. Nitric Oxide 41:146–156. https://doi.org/10.1016/j.niox.2014.03.001 Google Scholar
- 25.Shakeri M, Cottrell JJ, Wilkinson S, Ringuet M et al (2018) Betaine and antioxidants improve growth performance, breast muscle development and ameliorate thermoregulatory responses to cyclic heat exposure in broiler chickens. Animals (Basel) 25(8):E162. https://doi.org/10.3390/ani8100162 Google Scholar
- 26.Giriş M, Doğru-Abbasoğlu S, Soluk-Tekkeşin M, Olgaç V, Uysal M (2018) Effect of betaine treatment on the regression of existing hepatic triglyceride accumulation and oxidative stress in rats fed on high fructose diet. Gen Physiol Biophys 37:563–570. https://doi.org/10.4149/gpb_2018005 Google Scholar