Carboxy-terminal fragment of amyloid precursor protein mediates lipid droplet accumulation upon γ-secretase inhibition.
Biochem Biophys Res Commun
; 570: 137-142, 2021 09 17.
Article
em En
| MEDLINE
| ID: mdl-34280617
ABSTRACT
γ-Secretase is a protease catalysing the proteolysis of type-I membrane proteins usually after precedent ectodomain shedding of the respective protein substrates. Since proteolysis of membrane proteins is involved in fundamental cellular signaling pathways, dysfunction of γ-secretase can have significant impact on cellular metabolism and differentiation. Here, we examined the role of γ-secretase in cellular lipid metabolism using neuronally differentiated human SH-SY5Y cells. The pharmacological inhibition of γ-secretase induced lipid droplet (LD) accumulation. The LD accumulation was significantly attenuated by preventing the accumulation of C-terminal fragment of the amyloid precursor protein (APP-CTF), which is a direct substrate of γ-secretase. Additionally, LD accumulation upon γ-secretase inhibition was not induced in APP-knock out (APP-KO) mouse embryonic fibroblasts (MEFs), suggesting significant involvement of APP-CTF accumulation in LD accumulation upon γ-secretase inhibition. On the other hand, γ-secretase inhibition-dependent cholesterol accumulation was not attenuated by inhibition of APP-CTF accumulation in the differentiated SH-SY5Y cells nor in APP-KO MEFs. These results suggest that γ-secretase inhibition can induce accumulation of LD and cholesterol differentially via APP-CTF accumulation.
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Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Precursor de Proteína beta-Amiloide
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Secretases da Proteína Precursora do Amiloide
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Gotículas Lipídicas
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article