TY  - JOUR
AU  - Tovilović-Kovačević, Gordana
AU  - Ristić, Biljana
AU  - Šiljić, Marina
AU  - Nikolić, Valentina
AU  - Kravić-Stevović, Tamara
AU  - Dulović, Marija
AU  - Milenković, Marina
AU  - Knežević, Aleksandra
AU  - Bošnjak, Mihajlo
AU  - Bumbaširević, Vladimir
AU  - Stanojević, Maja
AU  - Trajković, Vladimir
PY  - 2013
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6345
AB  - 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.
PB  - Elsevier Masson SAS
T2  - Microbes and Infection
T1  - mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells
IS  - 8-9
VL  - 15
DO  - 10.1016/j.micinf.2013.04.012
SP  - 615
EP  - 624
ER  - 

@article{
author = "Tovilović-Kovačević, Gordana and Ristić, Biljana and Šiljić, Marina and Nikolić, Valentina and Kravić-Stevović, Tamara and Dulović, Marija and Milenković, Marina and Knežević, Aleksandra and Bošnjak, Mihajlo and Bumbaširević, Vladimir and Stanojević, Maja and Trajković, Vladimir",
year = "2013",
abstract = "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.",
publisher = "Elsevier Masson SAS",
journal = "Microbes and Infection",
title = "mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells",
number = "8-9",
volume = "15",
doi = "10.1016/j.micinf.2013.04.012",
pages = "615-624"
}

Tovilović-Kovačević, G., Ristić, B., Šiljić, M., Nikolić, V., Kravić-Stevović, T., Dulović, M., Milenković, M., Knežević, A., Bošnjak, M., Bumbaširević, V., Stanojević, M.,& Trajković, V.. (2013). mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells. in Microbes and Infection
Elsevier Masson SAS., 15(8-9), 615-624.
https://doi.org/10.1016/j.micinf.2013.04.012

Tovilović-Kovačević G, Ristić B, Šiljić M, Nikolić V, Kravić-Stevović T, Dulović M, Milenković M, Knežević A, Bošnjak M, Bumbaširević V, Stanojević M, Trajković V. mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells. in Microbes and Infection. 2013;15(8-9):615-624.
doi:10.1016/j.micinf.2013.04.012 .

Tovilović-Kovačević, Gordana, Ristić, Biljana, Šiljić, Marina, Nikolić, Valentina, Kravić-Stevović, Tamara, Dulović, Marija, Milenković, Marina, Knežević, Aleksandra, Bošnjak, Mihajlo, Bumbaširević, Vladimir, Stanojević, Maja, Trajković, Vladimir, "mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells" in Microbes and Infection, 15, no. 8-9 (2013):615-624,
https://doi.org/10.1016/j.micinf.2013.04.012 . .