Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus
Само за регистроване кориснике
2015
Аутори
Stanojlović, Miloš R.Guševac, Ivana
Grković, Ivana
Martinović, Jelena
Mitrović, Nataša Lj.
Zarić, Marina
Horvat, Anica
Drakulić, Dunja R.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The present study attempted to investigate how chronic cerebral hypoperfusion (CCH) and repeated low-dose progesterone (P) treatment affect gene and protein expression, subcellular distribution of key apoptotic elements within protein kinase B (Akt) and extracellular signal-regulated kinases (Erk) signal transduction pathways, as well as neurodegenerative processes and behavior. The results revealed the absence of Erk activation in CCH in cytosolic and synaptosomal fractions, indicating a lower threshold of Akt activation in brain ischemia, while P increased their levels above control values. CCH induced an increase in caspase 3 (Casp 3) and poly (ADP-ribose) polymerase (PARP) gene and protein expression. However, P restored expression of examined molecules in all observed fractions, except for the levels of Casp 3 in synapses which highlighted its possible non-apoptotic or even protective function. Our study showed the absence of nuclear factor kappa-light-chain-enhancer of activated ...b cells (NF-kappa B) response to this type of ischemic condition and its strong activation under the influence of P. Further, the initial increase in the number of apoptotic cells and amount of DNA fragmentation induced by CCH was significantly reduced by P. Finally, P reversed the CCH-induced reduction in locomotor activity, while promoting a substantial decrease in anxiety-related behavior. Our findings support the concept that repeated low-dose post-ischemic P treatment reduces CCH-induced neurodegeneration in the hippocampus. Neuroprotection is initiated through the activation of investigated kinases and regulation of their downstream molecules in subcellular specific manner, indicating that this treatment may be a promising therapy for alleviation of CCH-induced pathologies. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
Кључне речи:
progesterone / chronic cerebral hypoperfusion / apoptosis / neurodegenerationИзвор:
Neuroscience, 2015, 311, 308-321Издавач:
- Elsevier
Финансирање / пројекти:
- Молекуларни механизми патофизиолошких промена у ћелијама централног нервног система и периферног ткива код сисара (RS-MESTD-Basic Research (BR or ON)-173044)
- Ћелијска и молекулска основа неуроинфламације: потенцијала циљна места за транслациону медицину и терапију (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41014)
DOI: 10.1016/j.neuroscience.2015.10.040
ISSN: 0306-4522; 1873-7544
PubMed: 26518459
WoS: 000366144000027
Scopus: 2-s2.0-84946210704
Колекције
Институција/група
VinčaTY - JOUR AU - Stanojlović, Miloš R. AU - Guševac, Ivana AU - Grković, Ivana AU - Martinović, Jelena AU - Mitrović, Nataša Lj. AU - Zarić, Marina AU - Horvat, Anica AU - Drakulić, Dunja R. PY - 2015 UR - https://vinar.vin.bg.ac.rs/handle/123456789/846 AB - The present study attempted to investigate how chronic cerebral hypoperfusion (CCH) and repeated low-dose progesterone (P) treatment affect gene and protein expression, subcellular distribution of key apoptotic elements within protein kinase B (Akt) and extracellular signal-regulated kinases (Erk) signal transduction pathways, as well as neurodegenerative processes and behavior. The results revealed the absence of Erk activation in CCH in cytosolic and synaptosomal fractions, indicating a lower threshold of Akt activation in brain ischemia, while P increased their levels above control values. CCH induced an increase in caspase 3 (Casp 3) and poly (ADP-ribose) polymerase (PARP) gene and protein expression. However, P restored expression of examined molecules in all observed fractions, except for the levels of Casp 3 in synapses which highlighted its possible non-apoptotic or even protective function. Our study showed the absence of nuclear factor kappa-light-chain-enhancer of activated b cells (NF-kappa B) response to this type of ischemic condition and its strong activation under the influence of P. Further, the initial increase in the number of apoptotic cells and amount of DNA fragmentation induced by CCH was significantly reduced by P. Finally, P reversed the CCH-induced reduction in locomotor activity, while promoting a substantial decrease in anxiety-related behavior. Our findings support the concept that repeated low-dose post-ischemic P treatment reduces CCH-induced neurodegeneration in the hippocampus. Neuroprotection is initiated through the activation of investigated kinases and regulation of their downstream molecules in subcellular specific manner, indicating that this treatment may be a promising therapy for alleviation of CCH-induced pathologies. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved. PB - Elsevier T2 - Neuroscience T1 - Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus VL - 311 SP - 308 EP - 321 DO - 10.1016/j.neuroscience.2015.10.040 ER -
@article{ author = "Stanojlović, Miloš R. and Guševac, Ivana and Grković, Ivana and Martinović, Jelena and Mitrović, Nataša Lj. and Zarić, Marina and Horvat, Anica and Drakulić, Dunja R.", year = "2015", abstract = "The present study attempted to investigate how chronic cerebral hypoperfusion (CCH) and repeated low-dose progesterone (P) treatment affect gene and protein expression, subcellular distribution of key apoptotic elements within protein kinase B (Akt) and extracellular signal-regulated kinases (Erk) signal transduction pathways, as well as neurodegenerative processes and behavior. The results revealed the absence of Erk activation in CCH in cytosolic and synaptosomal fractions, indicating a lower threshold of Akt activation in brain ischemia, while P increased their levels above control values. CCH induced an increase in caspase 3 (Casp 3) and poly (ADP-ribose) polymerase (PARP) gene and protein expression. However, P restored expression of examined molecules in all observed fractions, except for the levels of Casp 3 in synapses which highlighted its possible non-apoptotic or even protective function. Our study showed the absence of nuclear factor kappa-light-chain-enhancer of activated b cells (NF-kappa B) response to this type of ischemic condition and its strong activation under the influence of P. Further, the initial increase in the number of apoptotic cells and amount of DNA fragmentation induced by CCH was significantly reduced by P. Finally, P reversed the CCH-induced reduction in locomotor activity, while promoting a substantial decrease in anxiety-related behavior. Our findings support the concept that repeated low-dose post-ischemic P treatment reduces CCH-induced neurodegeneration in the hippocampus. Neuroprotection is initiated through the activation of investigated kinases and regulation of their downstream molecules in subcellular specific manner, indicating that this treatment may be a promising therapy for alleviation of CCH-induced pathologies. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.", publisher = "Elsevier", journal = "Neuroscience", title = "Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus", volume = "311", pages = "308-321", doi = "10.1016/j.neuroscience.2015.10.040" }
Stanojlović, M. R., Guševac, I., Grković, I., Martinović, J., Mitrović, N. Lj., Zarić, M., Horvat, A.,& Drakulić, D. R.. (2015). Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus. in Neuroscience Elsevier., 311, 308-321. https://doi.org/10.1016/j.neuroscience.2015.10.040
Stanojlović MR, Guševac I, Grković I, Martinović J, Mitrović NL, Zarić M, Horvat A, Drakulić DR. Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus. in Neuroscience. 2015;311:308-321. doi:10.1016/j.neuroscience.2015.10.040 .
Stanojlović, Miloš R., Guševac, Ivana, Grković, Ivana, Martinović, Jelena, Mitrović, Nataša Lj., Zarić, Marina, Horvat, Anica, Drakulić, Dunja R., "Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus" in Neuroscience, 311 (2015):308-321, https://doi.org/10.1016/j.neuroscience.2015.10.040 . .