Приказ основних података о документу
AMP-activated protein kinase inhibits MPP+-induced oxidative stress and apoptotic death of SH-SY5Y cells through sequential stimulation of Akt and autophagy.
dc.creator | Jovanović-Tucović, Maja | |
dc.creator | Harhaji-Trajković, Ljubica | |
dc.creator | Dulović, Marija | |
dc.creator | Tovilović-Kovačević, Gordana | |
dc.creator | Zogović, Nevena | |
dc.creator | Jeremić, Marija | |
dc.creator | Mandić, Miloš | |
dc.creator | Kostić, Vladimir | |
dc.creator | Trajković, Vladimir | |
dc.creator | Marković, Ivanka | |
dc.date.accessioned | 2019-10-03T07:28:25Z | |
dc.date.available | 2900-01-01 | |
dc.date.issued | 2019 | |
dc.identifier.issn | 0014-2999 | |
dc.identifier.uri | https://www.sciencedirect.com/science/article/pii/S0014299919306296?via%3Dihub | |
dc.identifier.uri | https://radar.ibiss.bg.ac.rs/handle/123456789/3482 | |
dc.description.abstract | We investigated the interplay between the intracellular energy sensor AMP-activated protein kinase (AMPK), prosurvival kinase Akt, oxidative stress, and autophagy in the cytotoxicity of parkinsonian neurotoxin 1-methyl-4-phenyl piridinium (MPP+) towards SH-SY5Y human neuroblastoma cells. MPP+-mediated oxidative stress, mitochondrial depolarization, and apoptotic cell death were associated with rapid (within 2 h) activation of AMPK, its target Raptor, and prosurvival kinase Akt. Antioxidants N-acetylcysteine and butylated hydroxyanisole suppressed MPP+-induced cytotoxicity, AMPK, and Akt activation. A genetic or pharmacological inhibition of AMPK increased MPP+-triggered production of reactive oxygen species and cell death, and diminished Akt phosphorylation, while AMPK activation protected SH-SY5Y cells from MPP+. On the other hand, genetic or pharmacological inactivation of Akt stimulated MPP+-triggered oxidative stress and neurotoxicity, but did not affect AMPK activation. At later time-points (16-24 h), MPP+ inhibited the main autophagy repressor mammalian target of rapamycin, which coincided with the increase in the levels of autophagy marker microtubule-associated protein 1 light-chain 3B. MPP+ also increased the concentration of a selective autophagic target sequestosome-1/p62 and reduced the levels of lysosomal-associated membrane protein 1 and cytoplasmic acidification, suggesting that MPP+-induced autophagy was coupled with a decrease in autophagic flux. Nevertheless, further pharmacological inhibition of autophagy sensitized SH-SY5Y cells to MPP+-induced death. Antioxidants and AMPK knockdown reduced, whereas genetic inactivation of Akt potentiated neurotoxin-triggered autophagy. These results suggest that MPP+-induced oxidative stress stimulates AMPK, which protects SH-SY5Y cells through early activation of antioxidative Akt and late induction of cytoprotective autophagy. | en |
dc.relation | info:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41025/RS// | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175090/RS// | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173053/RS// | |
dc.rights | restrictedAccess | |
dc.source | European Journal of Pharmacology | |
dc.subject | AMPK | |
dc.subject | Akt | |
dc.subject | Autophagy | |
dc.subject | MPP+ | |
dc.subject | Neurons | |
dc.subject | Oxidative stress | |
dc.title | AMP-activated protein kinase inhibits MPP+-induced oxidative stress and apoptotic death of SH-SY5Y cells through sequential stimulation of Akt and autophagy. | en |
dc.type | article | en |
dc.rights.license | ARR | |
dcterms.abstract | Зоговић, Невена; Дуловић, Марија; Мандић, Милош; Трајковић, Владимир; Јовановић-Туцовић, Маја; Хархаји Трајковић, Љубица; Товиловић-Ковачевић, Гордана; Јеремић, Марија; Костић, Владимир; Марковић, Иванка; | |
dc.rights.holder | © 2019 Elsevier B.V. | |
dc.citation.volume | 863 | |
dc.identifier.doi | 10.1016/j.ejphar.2019.172677 | |
dc.identifier.pmid | 31542478 | |
dc.identifier.scopus | 2-s2.0-85072619805 | |
dc.identifier.wos | 000491966400008 | |
dc.citation.apa | Jovanovic-Tucovic, M., Harhaji-Trajkovic, L., Dulovic, M., Tovilovic-Kovacevic, G., Zogovic, N., Jeremic, M., et al. (2019). AMP-activated protein kinase inhibits MPP+-induced oxidative stress and apoptotic death of SH-SY5Y cells through sequential stimulation of Akt and autophagy. European Journal of Pharmacology, 863, 172677. | |
dc.citation.vancouver | Jovanovic-Tucovic M, Harhaji-Trajkovic L, Dulovic M, Tovilovic-Kovacevic G, Zogovic N, Jeremic M, Mandic M, Kostic V, Trajkovic V, Markovic I. AMP-activated protein kinase inhibits MPP+-induced oxidative stress and apoptotic death of SH-SY5Y cells through sequential stimulation of Akt and autophagy. Eur J Pharmacol. 2019;863:172677. | |
dc.citation.spage | 172677 | |
dc.type.version | publishedVersion | |
dc.citation.rank | M22 |