Evidence Details for Gpx4
PMID Title Journal Year Abstract
34405366 Scalp Acupuncture Protects Against Neuronal Ferroptosis by Activating The p62-Keap1-Nrf2 Pathway in Rat Models of Intracranial Haemorrhage. J Mol Neurosci. 2022 Jan;72(1):82-96. doi: 10.1007/s12031-021-01890-y. Epub 2021 Aug 17. 2022 Jan Intracerebral haemorrhage (ICH) can be a catastrophic event; even if the initial stages of the pathology were well-managed, a number of patients experience varied residual neurological deficits following the insult. Ferroptosis is a recently identified type of cell demise which is tightly linked to the neurological impairment associated with ICH. In the current work, the prophylactic impact of scalp acupuncture (SA) therapy on autologous blood injection murine models of ICH was investigated in order to establish whether SA could mitigate the secondary damage arising following ICH by moderating ferroptosis. The pathophysiological mechanisms associated with this process were also explored. Ludmila Belayev tests were utilised for the characterisation of neurological damage. Haematoxylin-eosin staining was employed in order to determine the cerebral impact of the induced ICH. Malondialdehyde (MDA) and iron titres in peri-haemorrhagic cerebral tissues were appraised using purchased assay kits. Transmission electron microscopy delineated mitochondrial appearances within nerve cell bodies from the area of haemorrhage. Western blotting techniques were utilised to assay the degree of protein expression of NeuN, sequestosome 1 (p62), nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1). The frequencies of Nrf2, GPX4 and FTH1 positive cells, respectively, were documented with immunohistochemical staining. The results demonstrated that therapy with SA after ICH mitigated MDA and iron sequestration, diminished the appearance of contracted mitochondria with increased outer mitochondrial membrane diameter within the nerve cell bodies, and suppressed neuronal ferroptosis. The pathways responsible for these effects may encompass amplified p62, Nrf2, GPX4 and FTH1 expression, together with decreased Keap1 expression. Application of SA reduced identified neurobehavioural abnormalities after ICH; no disparities were observed between the consequences of SA therapy and deferoxamine delivery. It can be surmised that intervention with SA enhanced recovery after ICH by triggering the antioxidant pathway, p62/Keap1/Nrf2, and causing FTH1 and GPX4 upregulation, factors that participate in diminishing excess iron and thus in mitigating lipid peroxidation insults arising from ferroptosis following ICH."

Evidence Sentence: Western blotting techniques were utilised to assay the degree of protein expression of NeuN, sequestosome 1 (p62), nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1).
Evidence Sentence: The frequencies of Nrf2, GPX4 and FTH1 positive cells, respectively, were documented with immunohistochemical staining.
Evidence Sentence: The pathways responsible for these effects may encompass amplified p62, Nrf2, GPX4 and FTH1 expression, together with decreased Keap1 expression.
Evidence Sentence: It can be surmised that intervention with SA enhanced recovery after ICH by triggering the antioxidant pathway, p62/Keap1/Nrf2, and causing FTH1 and GPX4 upregulation, factors that participate in diminishing excess iron and thus in mitigating lipid peroxidation insults arising from ferroptosis following ICH.
Evidence Sentence: SA Treatment Alleviates ICH-Induced MDA Accumulation by Increasing GPX4 Expression
Evidence Sentence: GPX4 is a key participant in oxidative stress equilibrium (Li et al.
Evidence Sentence: ); following ICH, GPX4 titres are diminished, thus aggravating the insult caused by ferroptosis lipid peroxidation (Wu et al.
Evidence Sentence: In order to establish the association between the accretion of GPX4 and MDA in the ICH model, GPX4-positive cells were identified.
Evidence Sentence: Immunopositivity for GPX4 implied that GPX4 levels diminished 6 h and 3 days following ICH but rose following therapy with SA (Fig.
Evidence Sentence: According to the Western blot results, upregulation of GPX4 expression was present following SA when judged against the ICH cohort for the various time junctures (Figs.
Evidence Sentence: In combination, these data infer that SA may diminish the oxidative stress damage precipitated by ICH by amplifying GPX4 expression.
Evidence Sentence: SA Treatment may Increase FTH1 and GPX4 Levels by Enhancing Nuclear Accumulation of Nrf2
Evidence Sentence: Within the context of oxidative stress, Nrf2 is an essential moderator (Kang and Tang ); its vital downstream proteins include GPX4 and FTH1.
Evidence Sentence: In order to determine whether SA therapy elevates FTH1 and GPX4 concentrations via nuclear Nrf2 accretion, immunohistochemical techniques were utilised to assay cerebral tissue Nrf2 immunopositivity.
Evidence Sentence: Concomitantly, the immunopositivity data with respect to GPX4 and FTH1 were in keeping with the changes in the Nrf2 titres (Fig.
Evidence Sentence: Western blotting was used to assay the degree of protein expression of both Nrf2 and the downstream transcripts, GPX4 and FTH1; the results supported the immunopositivity data (Fig.
Evidence Sentence: These findings indicate that FTH1 and GPX4 levels are elevated by SA via the promotion of nuclear Nrf2 accretion.