T0901317, an Agonist of Liver X Receptors, Attenuates Neuronal Apoptosis in Early Brain Injury after Subarachnoid Hemorrhage in Rats via Liver X Receptors/Interferon Regulatory Factor/P53 Upregulated Modulator of Apoptosis/Dynamin-1-Like Protein Pathway

Jiaxing Dai, Shancai Xu, Takeshi Okada, Yu Liu, Gang Zuo, Jiping Tang, John H. Zhang, Huaizhang Shi

Research output: Contribution to journalArticlepeer-review

Abstract

METHODS: Subarachnoid hemorrhage (SAH) models of Sprague-Dawley rats were established with perforation method. T0901317 was injected intraperitoneally 1-hour post-SAH. GSK2033, an inhibitor of LXRs, and interferon regulatory factor (IRF-1) CRISPR activation were injected intracerebroventricularly to evaluate potential signaling pathway. The severity of SAH, neurobehavior test in both short- and long-term and apoptosis was measured with Western blot and immunofluorescence staining.

RESULTS: Expression of LXR- α and IRF-1 increased and peaked at 24 h post-SAH, while LXR- β remained unaffected in SAH+vehicle group compared with Sham group. Post-SAH T0901317 treatment attenuated neuronal impairments in both short- and long-term and decreased neuronal apoptosis, the expression of IRF-1, P53 upregulated modulator of apoptosis (PUMA), dynamin-1-like protein (Drp1), Bcl-2-associated X protein (Bax) and cleaved caspase-3, and increasing B-cell lymphoma 2 (Bcl-2) at 24 h from modeling. GSK2033 inhibited LXRs and reversed T0901317's neuroprotective effects. IRF-1 CRISPR activation upregulated the expression of IRF-1 and abolished the treatment effects of T0901317.

CONCLUSION: T0901317 attenuated neuronal apoptosis via LXRs/IRF-1/PUMA/Drp1 pathway in SAH rats.

Original languageEnglish
Article number8849131
JournalOxidative Medicine and Cellular Longevity
Volume2021
DOIs
StatePublished - May 21 2021

ASJC Scopus Subject Areas

  • Biochemistry
  • Aging
  • Cell Biology

Keywords

  • Liver X Receptors/metabolism
  • Signal Transduction
  • Humans
  • Rats
  • Male
  • Rats, Sprague-Dawley
  • Brain Injuries/genetics
  • Animals
  • Sulfonamides/pharmacology
  • Dynamin I/metabolism
  • Hydrocarbons, Fluorinated/pharmacology
  • Apoptosis
  • Subarachnoid Hemorrhage/drug therapy

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