[Induction of the endoplasmic reticulum stress in conditions of acid-base imbalance in human cells of T-lymphoblastic leukemia]

Patol Fiziol Eksp Ter. 2012 Jul-Sep:(3):87-93.
[Article in Russian]

Abstract

Endoplasmic reticulum stress - typical molecular pathophysiological process that underlies many cardiovascular, endocrine and other diseases. Violations of the protein conformational maturation processes in the endoplasmic reticulum can cause proteotoxic stress. Compensatory mechanisms are activated in response to ER stress include increased expression of enzymes involved in the formation of disulfide bonds in proteins. The sulfhydryl groups oxidation in the electron transport chain (PDI-ERO1-O2) is associated with reactive oxygen species (ROS) generation. Increased activity of oxidoreductase ERO1 could be one of the mechanisms of oxidative stress - however, a direct relationship of ER stress with the overproduction of ROS remains a subject of debate. In this study we have shown that induced by dithiothreitol (DTT) violation of the redox balance with low ROS production leads to the endoplasmic reticulum stress in Jurkat cells. ER-stress in these cells is not associated with increased ROS production, DTT treatment leads to induction of apoptosis. Modulation of intracellular levels of ROS can influence the apoptosis-inducing effects of ER-stress. Given the possible involvement of ROS in the generation of disulfide bonds, the role of ROS in ER stress may be a modulation of disulfide proteome including client proteins.

Publication types

  • English Abstract

MeSH terms

  • Acid-Base Imbalance / chemically induced
  • Acid-Base Imbalance / metabolism*
  • Apoptosis / drug effects
  • Cell Culture Techniques
  • Dithiothreitol / pharmacology
  • Dose-Response Relationship, Drug
  • Endoplasmic Reticulum / drug effects*
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum Stress / drug effects*
  • Flow Cytometry
  • Homocysteine / pharmacology
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Jurkat Cells
  • Microscopy, Confocal
  • Reactive Oxygen Species / metabolism
  • Unfolded Protein Response / drug effects

Substances

  • Reactive Oxygen Species
  • Homocysteine
  • Dithiothreitol