Vitamin B12 Protects from Thiol Antioxidant Toxicity

Vitamin B12 Protects from Thiol Antioxidant Toxicity

  • Research Stash
  • News
  • 3.9K

A team of researchers at the Indian Institute of Science Education and Research (IISER), Mohali has revealed that the thiol reducing agent Dithiothreitol (DTT) causes toxicity by reducing the levels of an important regulatory molecule known as S-adenosylmethionine, and vitamin B12 could protect against this toxicity. The results of this study on the C. elegans (roundworms) model system have been published in the journal eLife.

Animal and plant cells synthesize a significant fraction of their proteins in a cellular compartment known as the Endoplasmic Reticulum (ER). The ER provides an oxidative environment required for the proper assembly of proteins. There are many small chemical molecules that can change the environment of the ER and could affect the proper assembling of proteins. One such molecule is DTT, a thiol antioxidant that researchers often use to specifically target ER compartment to learn more about its role. Research suggests that DTT works by disturbing the complex chemical environment present in the endoplasmic reticulum, which is required for the proteins to assemble properly. However, it is not understood whether DTT can modulate any other compartment of the cell as well.

“DTT possesses antioxidant properties, and therefore, it becomes even more critical to characterize its effects on the physiology of the cell completely. Therefore, we aimed to study the effects of DTT on the cellular physiology of an organism using the millimeter-long roundworm Caenorhabditis elegans,” says Dr. Jogender Singh, Ramalingaswami Re-entry Fellow and Assistant Professor at the Department of Biological Sciences, IISER, Mohali.

While studying DTT toxicity, the research team serendipitously observed that DTT toxicity in C. elegans was highly dependent on its bacterial diet. They discovered vitamin B12 as the bacterial metabolite that could reduce the toxic effects of DTT. Further, the research team also discovered that DTT resulted in the depletion of the important regulatory molecule S-adenosylmethionine in C. elegans. Because vitamin B12 is involved in the synthesis of methionine, which is a precursor for S-adenosylmethionine, it made sense why vitamin B12 reduced DTT toxicity.

In a cell, the synthesis of methionine and S-adenosylmethionine takes place in the cytoplasm, which is a thick solution that fills the cell and excludes the endoplasmic reticulum. Therefore, according to this study, the chemical reaction that DTT is targeting occurs outside the endoplasmic reticulum. “The primary reason for the toxic effects of DTT lies outside the endoplasmic reticulum! These results provide a new mechanism of action of DTT on cell physiology and suggest that DTT should be reconsidered for use in endoplasmic reticulum studies,” says Dr. Singh.

The study demonstrates that DTT can be used to modulate the levels of S-adenosylmethionine. “Since reduced levels of S-adenosylmethionine are associated with better health and lifespan in a variety of organisms, DTT could have health-promoting effects when administered in small doses,” says Dr. Singh.

“It will be intriguing to test whether, at non-toxic concentrations, DTT could have health-improving effects,” he added.

The study has provided new insights into the usage of antioxidants, and might help to understand the functionality of other thiol antioxidants, some of which are used as food supplements.

If you liked this article, then please subscribe to our YouTube Channel for the latest Science & Tech news. You can also find us on Twitter & Facebook

While studying DTT toxicity, the research team serendipitously observed that DTT toxicity in C. elegans was highly dependent on its bacterial diet. They discovered vitamin B12 as the bacterial metabolite that could reduce the toxic effects of DTT. Further, the research team also discovered that DTT resulted in the depletion of the important regulatory molecule S-adenosylmethionine in C. elegans. Because vitamin B12 is involved in the synthesis of methionine, which is a precursor for S-adenosylmethionine, it made sense why vitamin B12 reduced DTT toxicity.

In a cell, the synthesis of methionine and S-adenosylmethionine takes place in the cytoplasm, which is a thick solution that fills the cell and excludes the endoplasmic reticulum. Therefore, according to this study, the chemical reaction that DTT is targeting occurs outside the endoplasmic reticulum. “The primary reason for the toxic effects of DTT lies outside the endoplasmic reticulum! These results provide a new mechanism of action of DTT on cell physiology and suggest that DTT should be reconsidered for use in endoplasmic reticulum studies,” says Dr. Singh.

The study demonstrates that DTT can be used to modulate the levels of S-adenosylmethionine. “Since reduced levels of S-adenosylmethionine are associated with better health and lifespan in a variety of organisms, DTT could have health-promoting effects when administered in small doses,” says Dr. Singh.

“It will be intriguing to test whether, at non-toxic concentrations, DTT could have health-improving effects,” he added.

The study has provided new insights into the usage of antioxidants, and might help to understand the functionality of other thiol antioxidants, some of which are used as food supplements.

If you liked this article, then please subscribe to our YouTube Channel for the latest Science & Tech news. You can also find us on Twitter & Facebook

" }
Drug-Coated Bone Implants May Help Tackle Post-Surgery Infections

Drug-Coated Bone Implants May Help Tackle Post-Surgery Infections

Researchers have now come up with a method to localize the drug delivery to the surgery site. This has been achieved by modifying the surface of metallic implants by loading them with an antibacterial drug that gets released gradually over a period of one week at the implant site to prevent infections.

  • News
  • 1.5K
Read more
Researchers Develop Method for Manufacturing Optical Components

Researchers Develop Method for Manufacturing Optical Components

Researchers from the Council for Scientific and Industrial Research-Central Scientific Instruments Organization Chandigarh and Indian Institute of Technology Delhi have developed a method that would help in the manufacturing of optical components including simple shape optics to freeform optics by ultra-precision machining process and various related issues.

  • News
  • 1.8K
Read more
Researchers Develop ‘Hyperelastic Model’ To Understand Brain Injuries

Researchers Develop ‘Hyperelastic Model’ To Understand Brain Injuries

Indian Institute of Technology Madras researchers developed an analysis-driven ‘hyperelastic’ model in calculating the stress and strain experienced by the brain due to blunt force injury and lesion growth

  • News
  • 1.5K
Read more

Internet is huge! Help us find great content

Newsletter

Never miss a thing! Sign up for our newsletter to stay updated.

About

Research Stash is a curated collection of tools and News for S.T.E.M researchers

Have any questions or want to partner with us? Reach us at hello@researchstash.com

Navigation

Submit