IndraLab

Statements


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"To determine whether a decrease in UCH-L1 exacerbates h-IAPP-induced apoptosis, we transfected INS 832/13 cells with UCH-L1 siRNA or scramble (25 nmol/l, 36 h) and transduced these cells with h-IAPP or r-IAPP adenoviruses at 300 MOI for 30 h. Under these conditions, neither UCH-L1 siRNA nor h-IAPP alone induced cell death as illustrated by cleaved caspase-3 and cleaved PARP levels or caspase-3 activity (data not shown)."

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"The caspase mediated apoptosis in E-64-treated fibroblasts was reversed by transfection with a UCH-L1 plasmid, and increased after downregulation of UCH-L1 by siRNA, suggesting that UCH-L1 deficiency and impairment of the ubiquitin dependent protein degradation pathway can contribute to the increased cell death observed in many lysosomal storage disorders."

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"Thus, down-regulation of Uch-L1 induces the aggregation of ubiquitinated proteins and promotes cell death in neurons."

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"Down-regulation of endogenous UCHL1 in mouse N2a neuroblastoma cells increases cell death induced by oxygen-glucose deprivation."

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"Mutation of the C152 CyPG adduction site of UCH-L1, the site identified with conformational change of the protein with CyPG adduction, afforded protection from 15dPGJ2 induced cell death in primary cortical neurons."

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"The CTTDelta4 truncation provides a useful new tool for studying how UCH-L1 misfolding and dysfunction lead to protein instability and cell death, which pathways are involved, and what measures can be taken to reduce or prevent toxicity."