• BMB Reports
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• v.55 no.10
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• pp.494-499
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• 2022

PTEN-induced putative kinase 1 (PINK1) is a serine/threonine kinase that phosphorylates several substrates and exerts neuroprotective effects against stress-induced apoptotic cell death. Mutations in PINK1 have been linked to autosomal recessive forms of Parkinson's disease (PD). Mitophagy is a type of autophagy that selectively promotes mitochondrial turnover and prevents the accumulation of dysfunctional mitochondria to maintain cellular homeostasis. Toll-interacting protein (Tollip) was initially identified as a negative regulator of IL-1β receptor signaling, suppressing inflammatory TLR signaling cascades. Recently, Tollip has been reported to play a role in autophagy and is implicated in neurodegeneration. In this study, we determined whether Tollip was functionally linked to PINK1-mediated mitophagy. Our results demonstrated that Tollip promoted the mitochondrial processing of PINK1 and altered the localization of PINK1, predominantly to the cytosol. This action was attributed to increased binding of PINK1 to mitochondrial processing peptidase β (MPPβ) and the subsequent increase in MPPβ-mediated mitochondrial PINK1 cleavage. Furthermore, Tollip suppressed mitophagy following carbonyl cyanide m-chlorophenylhydrazone-induced mitochondrial dysfunction. These findings suggest that Tollip inhibits mitophagy via the PINK1/parkin pathway upon mitochondrial damage, leading to the blockade of PINK1-mediated neuroprotection.

• Animal Bioscience
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• v.37 no.2
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• pp.303-314
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• 2024

Objective: Rutin, also called vitamin P, is a flavonoids from plants. Previous studies have indicated that rutin can alleviate the injury of tissues and cells by inhibiting oxidative stress and ameliorating inflammation. There is no report on the protective effects of rutin on goat rumen epithelial cells (GRECs) at present. Hence, we investigated whether rutin can alleviate lipopolysaccharide (LPS)-induced damage in GRECs. Methods: GRECs were cultured in basal medium or basal medium containing 1 ㎍/mL LPS, or 1 ㎍/mL LPS and 20 ㎍/mL rutin. Six replicates were performed for each group. After 3-h culture, the GRECs were harvested to detect the relevant parameters. Results: Rutin significantly enhanced the cell activity (p<0.05) and transepithelial electrical resistance (TEER) (p<0.01) and significantly reduced the apoptosis rate (p<0.05) of LPS-induced GRECs. Rutin significantly increased superoxide dismutase, glutathione peroxidase, and catalase activity (p<0.01) and significantly decreased lactate dehydrogenase activity and reactive oxygen species and malondialdehyde (MDA) levels in LPS-induced GRECs (p<0.01). The mRNA and protein levels of interleukin 6 (IL-6), IL-1β, and C-X-C motif chemokine ligand 8 (CXCL8) and the mRNA level of tumor necrosis factor-α (TNF-α) and chemokine C-C motif ligand 5 (CCL5) were significantly increased in LPS-induced GRECs (p<0.05 or p<0.01), while rutin supplementation significantly decreased the mRNA and protein levels of IL-6, TNF-α, and CXCL8 in LPS-induced GRECs (p<0.05 or p<0.01). The mRNA level of toll-like receptor 2 (TLR2), and the mRNA and protein levels of TLR4 and nuclear factor κB (NF-κB) was significantly improved in LPS-induced GRECs (p<0.05 or p<0.01), whereas rutin supplementation could significantly reduce the mRNA and protein levels of TLR4 (p<0.05 or p<0.01). In addition, rutin had a tendency of decreasing the protein levels of CXCL6, NF-κB, and inhibitor of nuclear factor kappa-B alpha (0.05