Skip to main content

Hyperhomocysteinemia causes ER stress and impaired autophagy that is reversed by Vitamin B supplementation.

Publication ,  Journal Article
Tripathi, M; Zhang, CW; Singh, BK; Sinha, RA; Moe, KT; DeSilva, DA; Yen, PM
Published in: Cell Death Dis
December 8, 2016

Hyperhomocysteinemia (HHcy) is a well-known risk factor for stroke; however, its underlying molecular mechanism remains unclear. Using both mouse and cell culture models, we have provided evidence that impairment of autophagy has a central role in HHcy-induced cellular injury in the mouse brain. We observed accumulation of LC3B-II and p62 that was associated with increased MTOR signaling in human and mouse primary astrocyte cell cultures as well as a diet-induced mouse model of HHcy, HHcy decreased lysosomal membrane protein LAMP2, vacuolar ATPase (ATP6V0A2), and protease cathepsin D, suggesting that lysosomal dysfunction also contributed to the autophagic defect. Moreover, HHcy increased unfolded protein response. Interestingly, Vitamin B supplementation restored autophagic flux, alleviated ER stress, and reversed lysosomal dysfunction due to HHCy. Furthermore, the autophagy inducer, rapamycin was able to relieve ER stress and reverse lysosomal dysfunction caused by HHcy in vitro. Inhibition of autophagy by HHcy exacerbated cellular injury during oxygen and glucose deprivation and reperfusion (OGD/R), and oxidative stress. These effects were prevented by Vitamin B co-treatment, suggesting that it may be helpful in relieving detrimental effects of HHcy in ischemia/reperfusion or oxidative stress. Collectively, these findings show that Vitamin B therapy can reverse defects in cellular autophagy and ER stress due to HHcy; and thus may be a potential treatment to reduce ischemic damage caused by stroke in patients with HHcy.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cell Death Dis

DOI

EISSN

2041-4889

Publication Date

December 8, 2016

Volume

7

Issue

12

Start / End Page

e2513

Location

England

Related Subject Headings

  • Vitamin B 12
  • TOR Serine-Threonine Kinases
  • Sequestosome-1 Protein
  • Reperfusion Injury
  • Oxygen
  • Oxidative Stress
  • Models, Biological
  • Microtubule-Associated Proteins
  • Mice, Inbred C57BL
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Tripathi, M., Zhang, C. W., Singh, B. K., Sinha, R. A., Moe, K. T., DeSilva, D. A., & Yen, P. M. (2016). Hyperhomocysteinemia causes ER stress and impaired autophagy that is reversed by Vitamin B supplementation. Cell Death Dis, 7(12), e2513. https://doi.org/10.1038/cddis.2016.374
Tripathi, Madhulika, Cheng Wu Zhang, Brijesh Kumar Singh, Rohit Anthony Sinha, Kyaw Thu Moe, Deidre Anne DeSilva, and Paul Michael Yen. “Hyperhomocysteinemia causes ER stress and impaired autophagy that is reversed by Vitamin B supplementation.Cell Death Dis 7, no. 12 (December 8, 2016): e2513. https://doi.org/10.1038/cddis.2016.374.
Tripathi M, Zhang CW, Singh BK, Sinha RA, Moe KT, DeSilva DA, et al. Hyperhomocysteinemia causes ER stress and impaired autophagy that is reversed by Vitamin B supplementation. Cell Death Dis. 2016 Dec 8;7(12):e2513.
Tripathi, Madhulika, et al. “Hyperhomocysteinemia causes ER stress and impaired autophagy that is reversed by Vitamin B supplementation.Cell Death Dis, vol. 7, no. 12, Dec. 2016, p. e2513. Pubmed, doi:10.1038/cddis.2016.374.
Tripathi M, Zhang CW, Singh BK, Sinha RA, Moe KT, DeSilva DA, Yen PM. Hyperhomocysteinemia causes ER stress and impaired autophagy that is reversed by Vitamin B supplementation. Cell Death Dis. 2016 Dec 8;7(12):e2513.

Published In

Cell Death Dis

DOI

EISSN

2041-4889

Publication Date

December 8, 2016

Volume

7

Issue

12

Start / End Page

e2513

Location

England

Related Subject Headings

  • Vitamin B 12
  • TOR Serine-Threonine Kinases
  • Sequestosome-1 Protein
  • Reperfusion Injury
  • Oxygen
  • Oxidative Stress
  • Models, Biological
  • Microtubule-Associated Proteins
  • Mice, Inbred C57BL
  • Mice