Autophagy modulates keratin-containing inclusion formation and apoptosis in cell culture in a context-dependent fashion

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Harada M, Strnad P, Toivola DM, Omary MB
Förläggare: ELSEVIER INC
Publiceringsår: 2008
Tidskrift: Experimental Cell Research
Tidskriftsakronym: EXP CELL RES
Volym: 314
Nummer: 8
Artikelns första sida, sidnummer: 1753
Artikelns sista sida, sidnummer: 1764
Antal sidor: 12
ISSN: 0014-4827


Abstrakt

The major pathways for protein degradation are the proteasomal and lysosomal systems. Derangement of protein degradation causes the formation of intracellular inclusions, and apoptosis and is associated with several diseases. We utilized hepatocyte-derived cell lines to examine the consequences of the cytoplasmic hepatocyte Mallory-Denk body-like inclusions on organelle organization, autophagy and apoptosis, and tested the hypothesis that autophagy affects inclusion turnover. Proteasome inhibitors (PIs) generate keratin-containing Mallory-Denk body-like inclusions in cultured cells and cause reorganization of mitochondria and other organelles, autophagy and apoptosis. In cultured hepatoma cells, caspase inhibition blocks PI-induced apoptosis but not inclusion formation or autophagy activation. Autophagy induction by rapamycin decreases the extent of PI-induced inclusions and apoptosis in Huh7 and OUMS29 cells. Surprisingly, blocking of autophagy sequestration by 3 methyl adenine or beclin 1 siRNA, but not bafilomycin A1 inhibition of autophagic degradation, also inhibits inclusion formation in the tested cells. Therefore, autophagy can be upstream of apoptosis and may promote or alleviate inclusion formation in cell culture in a context-dependent manner via putative autophagy-associated molecular triggers. Manipulation of autophagy may offer a strategy to address the importance of inclusion formation and its significance in inclusion-associated diseases. Published by Elsevier Inc.


Nyckelord

intermediate filaments, Mallory-Denk bodies

Senast uppdaterad 2019-08-12 vid 03:00