STIM1, STIM2, and PDI Participate in Cellular Fate Decisions in Low Energy Availability Induced by 3-NP in Male Rats

Neurotox Res. 2021 Oct;39(5):1459-1469. doi: 10.1007/s12640-021-00388-0. Epub 2021 Jun 26.


Impairment in the energetic function of mitochondria is seen in many neurologic disorders like neurodegeneration. It disrupts ATP production, gives rise to oxidative stress, and ultimately challenges the viability of neurons. In this situation, neural cells use complex crosstalk between various subcellular elements to make live-or-die decisions about their fate. This study aimed to describe a part of the molecular changes and the outcome of the cellular decision during an energy crisis in neural cells in a time-dependent manner in the striatum. Adult male rats were treated with single or multiple 3-nitropropionic acid (3-NP) doses, a mitochondrial toxin, for 1 to 5 days. We found that protein disulfide isomerase (PDI) activity was decreased on the third day and remained lower than the control group up to the fifth day. However, on the day 1 and day 2 of 3-NP treatment, the stromal interaction molecule (STIM) 1 and STIM2 significantly decreased. On the third day, STIM1 and STIM2 were increased and reached the level of controls and remained the same up to the fifth day. In this condition, cell death was significantly higher than the controls from the third day up to the fifth day. We also showed that even a single dose of 3-NP reduced the brain volume. These data suggest that the STIM1, STIM2, and PDI activity changes may be involved in the outcome of cellular fate decisions. It also suggests that cells may reduce STIM1 and STIM2 as a defense mechanism against low energy availability.

Keywords: 3-NP; PDI; STIM1; STIM2; Striatum.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Convulsants / toxicity
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism
  • Energy Metabolism / drug effects*
  • Energy Metabolism / physiology
  • Male
  • Nitro Compounds / toxicity*
  • Organ Size / drug effects
  • Organ Size / physiology
  • Propionates / toxicity*
  • Protein Disulfide-Isomerases / metabolism*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Stromal Interaction Molecule 1 / metabolism*
  • Stromal Interaction Molecule 2 / metabolism*


  • Convulsants
  • Nitro Compounds
  • Propionates
  • STIM2 protein, rat
  • Stim1 protein, rat
  • Stromal Interaction Molecule 1
  • Stromal Interaction Molecule 2
  • Protein Disulfide-Isomerases
  • 3-nitropropionic acid