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Impact of inhibition of the autophagy-lysosomal pathway on biomolecules carbonylation and proteome regulation in rat cardiac cells.

Abstract：

:Cells employ multiple defence mechanisms to sustain a wide range of stress conditions associated with accumulation of modified self-biomolecules leading to lipo- and proteotoxicity. One of such mechanisms involves activation of the autophagy-lysosomal pathway for removal and degradation of modified lipids, proteins and even organelles. Biomolecules carbonylation, an irreversible oxidative modification, occurs in a variety of pathological conditions and is generally viewed as a marker of oxidative stress. Here, we used a model of rat primary cardiac cells to elucidate the role of autophagy-lysosomal pathway in the turnover of carbonylated biomolecules. Cells treated with inhibitors of autophagy-lysosomal degradation and primed with a short pulse of mild nitroxidative stress were studied using fluorescent microscopy and accumulation of carbonylated biomolecules in droplets- or vesicle-like structures was observed. Furthermore, systems-wide analysis of proteome regulation using relative label free quantification approach revealed the most significant alterations in cells treated with protease inhibitors. Interestingly, down-regulation of insulin signalling was among the most enriched pathway, as revealed by functional annotation of regulated proteins.

journal_name

Redox Biol

journal_title

Redox biology

authors

Coliva G,Duarte S,Pérez-Sala D,Fedorova M

doi

10.1016/j.redox.2019.101123

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

101123

issn

2213-2317

pii

S2213-2317(18)31018-8

journal_volume

23

pub_type

杂志文章

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