Abstract
Heat-shock protein B (HSPB1) has a neuroprotective effect on brain injury and is a negative regulator of ferroptosis. Therefore, we infer that HSPB1 plays a protective role in hypoxic-ischemic (HI) brain damage by inhibiting ferroptosis. A neonatal rat model of hypoxic-ischemic (HI) brain damage was established. HSPB1 overexpression plasmid and the negative control were injected into the lateral ventricle of rats 48 h before HI brain damage surgery. HSPB1 and glucose-6-phosphate dehydrogenase (G6PD) levels, infarction rate, iron accumulation, apoptosis, and ferroptosis-related markers were estimated with the assistance of qRT-PCR, 2,3,5-triphenyl tetrazolium chloride (TTC) staining, Prussian blue staining, iron assay kit, TUNEL staining, and Western blot. In vitro, after transfection, HSPB1 and G6PD levels, oxygen-glucose deprivation (OGD)-mediated hippocampal neuron cell viability, apoptosis, iron content, and ferroptosis-related markers were assessed using qRT-PCR, MTT, flow cytometry, iron assay kit, and Western blot. HSPB1 and G6PD were overexpressed in the hippocampus tissues of HI rats. High expression of HSPB1 in HI rats lessened infarction rate and ferritin level, hindered iron accumulation and apoptosis, and promoted GPX4, SLC7A11, and TFR1 levels. In OGD-mediated hippocampal neuron cells, HSPB1 upregulation intensified the viability and repressed apoptosis and ferroptosis, whereas G6PD silencing reversed the effects of HSPB1 upregulation. We documented that HSPB1 overexpression unleashes neuroprotective effects via modulating G6PD expression, which offers a novel target for the prevention and treatment of HI brain damage.NEW & NOTEWORTHY HSPB1 and G6PD were overexpressed in the hippocampus tissues of HI rats. High expression of HSPB1 in HI rats mitigated infarction rate and iron accumulation. HSPB1 overexpression reduced ferritin level, attenuated apoptosis, yet augmented GPX4, SLC7A11, and TFR1 levels in the hippocampus tissues of HI rats. G6PD deletion impaired the protective role of HSPB1 overexpression against HI brain damage-induced ferroptosis.
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