TY - JOUR
T1 - 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
AU - Dai, Jiaxing
AU - Xu, Shancai
AU - Okada, Takeshi
AU - Liu, Yu
AU - Zuo, Gang
AU - Tang, Jiping
AU - Zhang, John H.
AU - Shi, Huaizhang
N1 - Publisher Copyright:
© 2021 Jiaxing Dai et al.
PY - 2021/5/21
Y1 - 2021/5/21
N2 - 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.
AB - 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.
KW - Liver X Receptors/metabolism
KW - Signal Transduction
KW - Humans
KW - Rats
KW - Male
KW - Rats, Sprague-Dawley
KW - Brain Injuries/genetics
KW - Animals
KW - Sulfonamides/pharmacology
KW - Dynamin I/metabolism
KW - Hydrocarbons, Fluorinated/pharmacology
KW - Apoptosis
KW - Subarachnoid Hemorrhage/drug therapy
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U2 - 10.1155/2021/8849131
DO - 10.1155/2021/8849131
M3 - Article
C2 - 34194609
SN - 1942-0900
VL - 2021
JO - Oxidative Medicine and Cellular Longevity
JF - Oxidative Medicine and Cellular Longevity
M1 - 8849131
ER -