Evidence Details for Keap1
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 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: ), the substrate adaptor p62 protein, also referred to as sequestosome 1, has an immediate impact on Nrf2 expression by attaching to Keap1.
Evidence Sentence: In order to further appreciate the pathways involved in the upregulation of Nrf2 following ICH, Western blot was utilised to assay the degree of expression of p62 and Keap1 proteins (Fig.
Evidence Sentence: In cerebral samples from the rats with ICH, p62 expression was elevated and Keap1 protein expression was diminished.
Evidence Sentence: Furthermore, in contrast to the ICH cohort, rats receiving SA therapy demonstrated heightened expression of p62 protein and reduced Keap1 protein expression on days 1 and 3, respectively, following ICH (Fig.
Evidence Sentence: The possibility of p62 attaching to Keap1 so as dislodge Nrf2, to suppress Nrf2 breakdown and to promote nuclear accretion, was then explored.
Evidence Sentence: Western blot data revealed a marked rise in Nrf2 titres in the immediate phase concomitant with the rise and fall in p62 and Keap1 concentrations, respectively (Fig.
Evidence Sentence: All these findings imply that the engagement of p62 and Keap1 underlies the nuclear amassment of Nrf2 in ferroptosis, and that therapy with SA may augment Nrf2 transcription by promoting the association between p62 and Keap1.
Evidence Sentence: Scalp Acupuncture Protects Against Neuronal Ferroptosis by Activating The p62-Keap1-Nrf2 Pathway in Rat Models of Intracranial Haemorrhage