Autophagy deficient melanocytes display a senescence associated secretory phenotype that includes oxidized lipid mediators.
Int J Biochem Cell Biol
; 81(Pt B): 375-382, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27732890
ABSTRACT
Autophagy is a recycling program which allows cells to adapt to metabolic needs and to stress. Defects in autophagy can affect metabolism, aging, proteostasis and inflammation. Autophagy pathway genes, including autophagy related 7 (Atg7), have been associated with the regulation of skin pigmentation, and autophagy defects disturb the biogenesis and transport of melanosomes in melanocytes as well as transfer and processing of melanin into keratinocytes. We have previously shown that mice whose melanocytes or keratinocytes lack Atg7 (and thus autophagy) as a result of specific gene knockout still retained functioning melanosome synthesis and transfer, and displayed only moderate reduction of pigmentation. In cell culture the Atg7 deficient melanocytes were prone to premature senescence and dysregulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling. To elucidate the biochemical basis of this phenotype, we performed a study on global gene expression, protein secretion and phospholipid composition in Atg7 deficient versus Atg7 expressing melanocytes. In cell culture Atg7 deficient melanocytes showed a pro-inflammatory gene expression signature and secreted higher levels of C-X-C motif chemokine ligand -1,-2,-10 and -12 (Cxcl1, Cxcl2, Cxcl10, Cxcl12), which are implicated in the pathogenesis of pigmentary disorders and expressed higher amounts of matrix metalloproteinases -3 and -13 (Mmp3, Mmp13). The analysis of membrane phospholipid composition identified an increase in the arachidonic- to linoleic acid ratio in the autophagy deficient cells, as well as an increase in oxidized phospholipid species that act as danger associated molecular patterns (DAMPs). The secretion of inflammation related factors suggests that autophagy deficient melanocytes display a senescence associated secretory phenotype (SASP), and we propose oxidized lipid mediators as novel components of this SASP.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
/
Metabolismo dos Lipídeos
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Proteína 7 Relacionada à Autofagia
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Melanócitos
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Int J Biochem Cell Biol
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China