mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells
2013
Аутори:
Tovilović-Kovačević, GordanaRistić, Biljana
Šiljić, Marina
Nikolić, Valentina
Kravić-Stevović, Tamara
Dulović, Marija
Milenković, Marina
Knežević, Aleksandra
Bošnjak, Mihajlo
Bumbaširević, Vladimir
Stanojević, Maja
Trajković, Vladimir
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2013 by Institut Pasteur
Метаподаци
Приказ свих података о документуАпстракт:
We investigated the role of autophagy, a stress-inducible lysosomal self-digestion of cellular components, in modulation of herpes simplex virus type 1 (HSV-1)-triggered death of U251 human glioma cells. HSV-1 caused apoptotic death in U251 cells, characterized by phosphatidylserine externalization, caspase activation and DNA fragmentation. HSV-1-induced apoptosis was associated with the induction of autophagic response, as confirmed by the conversion of cytosolic LC3-I to autophagosome-associated LC3-II, increase in intracellular acidification, presence of autophagic vesicles, and increase in proteolysis of the selective autophagic target p62. HSV-1-triggered autophagy was not associated with the significant increase in the expression of proautophagic protein beclin-1 or downregulation of the major autophagy suppressor mammalian target of rapamycin (mTOR). Moreover, the phosphorylation of mTOR and its direct substrate p70 S6 kinase was augmented by HSV-1 infection, while the mTOR stimulator Akt and inhibitor AMPK-activated protein kinase (AMPK) were accordingly activated and suppressed, respectively. An shRNA-mediated knockdown of the autophagy-essential LC3b, as well as pharmacological inhibition of autophagy with bafilomycin A1 or 3-methyladenine, markedly accelerated apoptotic changes and ensuing cell death in HSV-1-infected glioma cells. These data indicate that AMPK/Akt/mTOR-independent autophagy could prolong survival of HSV-1-infected U251 glioma cells by counteracting the coinciding apoptotic response.
Кључне речи:
HSV-1; Autophagy; Apoptosis; mTOR; AMP-activated protein kinase; AktИзвор:
Microbes and Infection, 2013, 15, 8-9, 615-624Финансирање / пројекти:
- Модулација сигналних путева који контролишу интрацелуларни енергетски баланс у терапији тумора и неуро-имуно-ендокриних поремећаја (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41025)
- Филогенетски приступ анализи молекуларне еволуције високо варијабилних вируса - коинфекције, интеракција вируса и домаћина (RS-MESTD-Basic Research (BR or ON)-175024)
- Улога аутофагије у регулацији смрти туморских ћелија (RS-MESTD-Basic Research (BR or ON)-173053)
DOI: 10.1016/j.micinf.2013.04.012
ISSN: 1286-4579
PubMed: 23669212