Low-level arsenic causes proteotoxic stress and not oxidative stress

Matthew Dodson, Montserrat Rojo de la Vega, Bryan Harder, Raul Castro-Portuguez, Silvia D. Rodrigues, Pak Kin Wong, Eli Chapman, Donna D. Zhang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Prolonged exposure to arsenic has been shown to increase the risk of developing a number of diseases, including cancer and type II diabetes. Arsenic is present throughout the environment in its inorganic forms, and the level of exposure varies greatly by geographical location. The current recommended maximum level of arsenic exposure by the EPA is 10 μg/L, but levels > 50–1000 μg/L have been detected in some parts of Asia, the Middle East, and the Southwestern United States. One of the most important steps in developing treatment options for arsenic-linked pathologies is to understand the cellular pathways affected by low levels of arsenic. Here, we show that acute exposure to non-lethal, low-level arsenite, an environmentally relevant arsenical, inhibits the autophagy pathway. Furthermore, arsenite-induced autophagy inhibition initiates a transient, but moderate ER stress response. Significantly, low-level arsenite exposure does not exhibit an increase in oxidative stress. These findings indicate that compromised autophagy, and not enhanced oxidative stress occurs early during arsenite exposure, and that restoring the autophagy pathway and proper proteostasis could be a viable option for treating arsenic-linked diseases. As such, our study challenges the existing paradigm that oxidative stress is the main underlying cause of pathologies associated with environmental arsenic exposure.

Original languageEnglish (US)
Pages (from-to)106-113
Number of pages8
JournalToxicology and Applied Pharmacology
Volume341
DOIs
StatePublished - Feb 15 2018

Fingerprint

Oxidative stress
Arsenic
Oxidative Stress
Autophagy
Pathology
Southwestern United States
Arsenicals
Middle East
Environmental Exposure
Medical problems
Type 2 Diabetes Mellitus
arsenite
Neoplasms

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Cite this

Dodson, M., de la Vega, M. R., Harder, B., Castro-Portuguez, R., Rodrigues, S. D., Wong, P. K., ... Zhang, D. D. (2018). Low-level arsenic causes proteotoxic stress and not oxidative stress. Toxicology and Applied Pharmacology, 341, 106-113. https://doi.org/10.1016/j.taap.2018.01.014
Dodson, Matthew ; de la Vega, Montserrat Rojo ; Harder, Bryan ; Castro-Portuguez, Raul ; Rodrigues, Silvia D. ; Wong, Pak Kin ; Chapman, Eli ; Zhang, Donna D. / Low-level arsenic causes proteotoxic stress and not oxidative stress. In: Toxicology and Applied Pharmacology. 2018 ; Vol. 341. pp. 106-113.
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Dodson, M, de la Vega, MR, Harder, B, Castro-Portuguez, R, Rodrigues, SD, Wong, PK, Chapman, E & Zhang, DD 2018, 'Low-level arsenic causes proteotoxic stress and not oxidative stress', Toxicology and Applied Pharmacology, vol. 341, pp. 106-113. https://doi.org/10.1016/j.taap.2018.01.014

Low-level arsenic causes proteotoxic stress and not oxidative stress. / Dodson, Matthew; de la Vega, Montserrat Rojo; Harder, Bryan; Castro-Portuguez, Raul; Rodrigues, Silvia D.; Wong, Pak Kin; Chapman, Eli; Zhang, Donna D.

In: Toxicology and Applied Pharmacology, Vol. 341, 15.02.2018, p. 106-113.

Research output: Contribution to journalArticle

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Dodson M, de la Vega MR, Harder B, Castro-Portuguez R, Rodrigues SD, Wong PK et al. Low-level arsenic causes proteotoxic stress and not oxidative stress. Toxicology and Applied Pharmacology. 2018 Feb 15;341:106-113. https://doi.org/10.1016/j.taap.2018.01.014