AMPK-regulated miRNA-210-3p is activated during ischaemic neuronal injury and modulates PI3K-p70S6K signalling.
AMP-Activated Protein Kinases
/ metabolism
Animals
Cerebral Cortex
/ pathology
Computational Biology
Enzyme Activation
Female
Ischemic Stroke
/ pathology
Male
Mice, Inbred C57BL
MicroRNAs
/ genetics
Neurons
/ pathology
PTEN Phosphohydrolase
/ metabolism
Phosphatidylinositol 3-Kinases
/ genetics
Polymerase Chain Reaction
Primary Cell Culture
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
/ metabolism
Ribosomal Protein S6
/ metabolism
Ribosomal Protein S6 Kinases, 70-kDa
/ genetics
Signal Transduction
AMPK
ischaemia
microRNA
neuronal injury
stroke
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
12
02
2021
received:
09
10
2020
accepted:
05
03
2021
pubmed:
12
3
2021
medline:
7
1
2022
entrez:
11
3
2021
Statut:
ppublish
Résumé
Progressive neuronal injury following ischaemic stroke is associated with glutamate-induced depolarization, energetic stress and activation of AMP-activated protein kinase (AMPK). We here identify a molecular signature associated with neuronal AMPK activation, as a critical regulator of cellular response to energetic stress following ischaemia. We report a robust induction of microRNA miR-210-3p both in vitro in primary cortical neurons in response to acute AMPK activation and following ischaemic stroke in vivo. Bioinformatics and reverse phase protein array analysis of neuronal protein expression changes in vivo following administration of a miR-210-3p mimic revealed altered expression of phosphatase and tensin homolog (PTEN), 3-phosphoinositide-dependent protein kinase 1 (PDK1), ribosomal protein S6 kinase (p70S6K) and ribosomal protein S6 (RPS6) signalling in response to increasing miR-210-3p. In vivo, we observed a corresponding reduction in p70S6K activity following ischaemic stroke. Utilizing models of glutamate receptor over-activation in primary neurons, we demonstrated that induction of miR-210-3p was accompanied by sustained suppression of p70S6K activity and that this effect was reversed by miR-210-3p inhibition. Collectively, these results provide new molecular insight into the regulation of cell signalling during ischaemic injury, and suggest a novel mechanism whereby AMPK regulates miR-210-3p to control p70S6K activity in ischaemic stroke and excitotoxic injury.
Substances chimiques
MIRN210 microRNA, mouse
0
MicroRNAs
0
Pdk1 protein, mouse
0
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
0
Ribosomal Protein S6
0
ribosomal protein S6, mouse
0
Ribosomal Protein S6 Kinases, 70-kDa
EC 2.7.11.1
ribosomal protein S6 kinase, 70kD, polypeptide 2
EC 2.7.11.1
AMP-Activated Protein Kinases
EC 2.7.11.31
PTEN Phosphohydrolase
EC 3.1.3.67
Pten protein, mouse
EC 3.1.3.67
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
710-728Informations de copyright
© 2021 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.
Références
Alessi, D. R., Kozlowski, M. T., Weng, Q. P., Morrice, N., & Avruch, J. (1998). 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro. Current Biology, 8, 69-81. https://doi.org/10.1016/S0960-9822(98)70037-5.
Anilkumar, U., Weisova, P., Dussmann, H., Concannon, C. G., Konig, H. G., & Prehn, J. H. (2013). AMP-activated protein kinase (AMPK)-induced preconditioning in primary cortical neurons involves activation of MCL-1. Journal of Neurochemistry, 124, 721-734. https://doi.org/10.1111/jnc.12108.
Arumugam, T. V., Baik, S. H., Balaganapathy, P., Sobey, C. G., Mattson, M. P., & Jo, D. G. (2018). Notch signaling and neuronal death in stroke. Progress in Neurobiology, 165-167, 103-116. https://doi.org/10.1016/j.pneurobio.2018.03.002.
Arumugam, T. V., Chan, S. L., Jo, D.-G., Yilmaz, G., Tang, S.-C., Cheng, A., Gleichmann, M., Okun, E., Dixit, V. D., Chigurupati, S., Mughal, M. R., Ouyang, X., Miele, L., Magnus, T., Poosala, S., Granger, D. N., & Mattson, M. P. (2006). Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke. Nature Medicine, 12, 621-623. https://doi.org/10.1038/nm1403.
Balendran, A., Currie, R., Armstrong, C. G., Avruch, J., & Alessi, D. R. (1999). Evidence that 3-phosphoinositide-dependent protein kinase-1 mediates phosphorylation of p70 S6 kinase in vivo at Thr-412 as well as Thr-252. Journal of Biological Chemistry, 274, 37400-37406. https://doi.org/10.1074/jbc.274.52.37400.
Belov Kirdajova, D., Kriska, J., Tureckova, J., & Anderova, M. (2020). Ischemia-triggered glutamate excitotoxicity from the perspective of glial cells. Frontiers in Cellular Neuroscience, 14, 51. https://doi.org/10.3389/fncel.2020.00051.
Biever, A., Valjent, E., & Puighermanal, E. (2015). Ribosomal protein S6 phosphorylation in the nervous system: From regulation to function. Frontiers in Molecular Neuroscience, 8, 75. https://doi.org/10.3389/fnmol.2015.00075.
Brennan-Minnella, A. M., Shen, Y., El-Benna, J., & Swanson, R. A. (2013). Phosphoinositide 3-kinase couples NMDA receptors to superoxide release in excitotoxic neuronal death. Cell Death & Disease, 4, e580. https://doi.org/10.1038/cddis.2013.111.
Calzavara, E., Chiaramonte, R., Cesana, D., Basile, A., Sherbet, G. V., & Comi, P. (2008). Reciprocal regulation of Notch and PI3K/Akt signalling in T-ALL cells in vitro. Journal of Cellular Biochemistry, 103, 1405-1412. https://doi.org/10.1002/jcb.21527.
Carling, D. (2004). The AMP-activated protein kinase cascade-a unifying system for energy control. Trends in Biochemical Sciences, 29, 18-24. https://doi.org/10.1016/j.tibs.2003.11.005.
Chagpar, R. B., Links, P. H., Pastor, M. C., Furber, L. A., Hawrysh, A. D., Chamberlain, M. D., & Anderson, D. H. (2010). Direct positive regulation of PTEN by the p85 subunit of phosphatidylinositol 3-kinase. Proceedings of the National Academy of Sciences, 107, 5471-5476. https://doi.org/10.1073/pnas.0908899107.
Chan, S. Y., & Loscalzo, J. (2010). MicroRNA-210: A unique and pleiotropic hypoxamir. Cell Cycle, 9, 1072-1083. https://doi.org/10.4161/cc.9.6.11006.
Chen, L. I., Yang, L., Yao, L., Kuang, X.-Y., Zuo, W.-J., Li, S., Qiao, F., Liu, Y.-R., Cao, Z.-G., Zhou, S.-L., Zhou, X.-Y., Yang, W.-T., Shi, J.-X., Huang, W., Hu, X., & Shao, Z.-M. (2018). Characterization of PIK3CA and PIK3R1 somatic mutations in Chinese breast cancer patients. Nature Communications, 9, 1357. https://doi.org/10.1038/s41467-018-03867-9.
Chou, C.-H., Shrestha, S., Yang, C.-D., Chang, N.-W., Lin, Y.-L., Liao, K.-W., Huang, W.-C., Sun, T.-H., Tu, S.-J., Lee, W.-H., Chiew, M.-Y., Tai, C.-S., Wei, T.-Y., Tsai, T.-R., Huang, H.-T., Wang, C.-Y., Wu, H.-Y., Ho, S.-Y., Chen, P.-R., … Huang, H.-D. (2018). miRTarBase update 2018: A resource for experimentally validated microRNA-target interactions. Nucleic Acids Research, 46, D296-D302. https://doi.org/10.1093/nar/gkx1067.
Concannon, C. G., Tuffy, L. P., Weisová, P., Bonner, H. P., Dávila, D., Bonner, C., Devocelle, M. C., Strasser, A., Ward, M. W., & Prehn, J. H. M. (2010). AMP kinase-mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis. The Journal of Cell Biology, 189, 83-94. https://doi.org/10.1083/jcb.200909166.
Concannon, C. G., Ward, M. W., Bonner, H. P., Kuroki, K., Tuffy, L. P., Bonner, C. T., Woods, I., Engel, T., Henshall, D. C., & Prehn, J. H. M. (2008). NMDA receptor-mediated excitotoxic neuronal apoptosis in vitro and in vivo occurs in an ER stress and PUMA independent manner. Journal of Neurochemistry, 105, 891-903. https://doi.org/10.1111/j.1471-4159.2007.05187.x.
Culmsee, C., Monnig, J., Kemp, B. E., & Mattson, M. P. (2001). AMP-activated protein kinase is highly expressed in neurons in the developing rat brain and promotes neuronal survival following glucose deprivation. Journal of Molecular Neuroscience: MN, 17, 45-58.10.1385/JMN:17:1:45.
Culmsee, C., Zhu, C., Landshamer, S., Becattini, B., Wagner, E., Pellecchia, M., Blomgren, K., & Plesnila, N. (2005). Apoptosis-inducing factor triggered by poly(ADP-ribose) polymerase and Bid mediates neuronal cell death after oxygen-glucose deprivation and focal cerebral ischemia. Journal of Neuroscience, 25, 10262-10272. https://doi.org/10.1523/JNEUROSCI.2818-05.2005.
Dang, K., & Myers, K. A. (2015). The role of hypoxia-induced miR-210 in cancer progression. International Journal of Molecular Sciences, 16, 6353-6372. https://doi.org/10.3390/ijms16036353.
Davila, D., Connolly, N. M., Bonner, H., Weisova, P., Dussmann, H., Concannon, C. G., Huber, H. J., & Prehn, J. H. (2012). Two-step activation of FOXO3 by AMPK generates a coherent feed-forward loop determining excitotoxic cell fate. Cell Death and Differentiation, 19, 1677-1688. https://doi.org/10.1038/cdd.2012.49.
Dharap, A., Bowen, K., Place, R., Li, L. C., & Vemuganti, R. (2009). Transient focal ischemia induces extensive temporal changes in rat cerebral microRNAome. Journal of Cerebral Blood Flow and Metabolism, 29, 675-687. https://doi.org/10.1038/jcbfm.2008.157.
Dirnagl, U., Iadecola, C., & Moskowitz, M. A. (1999). Pathobiology of ischaemic stroke: An integrated view. Trends in Neurosciences, 22, 391-397. https://doi.org/10.1016/S0166-2236(99)01401-0.
D'Orsi, B., Bonner, H., Tuffy, L. P., Dussmann, H., Woods, I., Courtney, M. J., Ward, M. W., & Prehn, J. H. (2012). Calpains are downstream effectors of bax-dependent excitotoxic apoptosis. Journal of Neuroscience, 32, 1847-1858. https://doi.org/10.1523/JNEUROSCI.2345-11.2012.
Gao, X., Qin, T., Mao, J., Zhang, J., Fan, S., Lu, Y., Sun, Z., Zhang, Q., Song, B. O., & Li, L. (2019). PTENP1/miR-20a/PTEN axis contributes to breast cancer progression by regulating PTEN via PI3K/AKT pathway. Journal of Experimental & Clinical Cancer Research, 38, 256. https://doi.org/10.1186/s13046-019-1260-6.
Gong, X., Wang, H., Ye, Y., Shu, Y., Deng, Y., He, X., Lu, G., & Zhang, S. (2016). miR-124 regulates cell apoptosis and autophagy in dopaminergic neurons and protects them by regulating AMPK/mTOR pathway in Parkinson's disease. American Journal of Translational Research, 8, 2127-2137.
Green, A. R. (2004). Protecting the brain: The search for a clinically effective neuroprotective drug for stroke. Critical Reviews in Neurobiology, 16, 91-97. https://doi.org/10.1615/CritRevNeurobiol.v16.i12.100.
Green, A. R., & Shuaib, A. (2006). Therapeutic strategies for the treatment of stroke. Drug Discov Today, 11, 681-693. https://doi.org/10.1016/j.drudis.2006.06.001.
Grego-Bessa, J., Bloomekatz, J., Castel, P., Omelchenko, T., Baselga, J., & Anderson, K. V. (2016). The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium. Elife, 5, e12034. https://doi.org/10.7554/eLife.12034.
Hann, S. S., Tang, Q., Zheng, F., Zhao, S., Chen, J., & Wang, Z. (2014). Repression of phosphoinositide-dependent protein kinase 1 expression by ciglitazone via Egr-1 represents a new approach for inhibition of lung cancer cell growth. Molecular Cancer, 13, 149. https://doi.org/10.1186/1476-4598-13-149.
Hardie, D. G. (2011). AMP-activated protein kinase: A cellular energy sensor with a key role in metabolic disorders and in cancer. Biochemical Society Transactions, 39, 1-13. https://doi.org/10.1042/BST0390001.
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012). AMPK: A nutrient and energy sensor that maintains energy homeostasis. Nature Reviews Molecular Cell Biology, 13, 251-262. https://doi.org/10.1038/nrm3311.
Hardie, D. G., Salt, I. P., Hawley, S. A., & Davies, S. P. (1999). AMP-activated protein kinase: An ultrasensitive system for monitoring cellular energy charge. The Biochemical Journal, 338(Pt 3), 717-722.
Hausenloy, D. J., Mocanu, M. M., & Yellon, D. M. (2004). Cross-talk between the survival kinases during early reperfusion: Its contribution to ischemic preconditioning. Cardiovascular Research, 63, 305-312. https://doi.org/10.1016/j.cardiores.2004.04.011.
Hennessy, B. T., Lu, Y., Gonzalez-Angulo, A. M., Carey, M. S., Myhre, S., Ju, Z., Davies, M. A., Liu, W., Coombes, K., Meric-Bernstam, F., Bedrosian, I., McGahren, M., Agarwal, R., Zhang, F., Overgaard, J., Alsner, J., Neve, R. M., Kuo, W.-L., Gray, J. W., … Mills, G. B. (2010). A technical assessment of the utility of reverse phase protein arrays for the study of the functional proteome in non-microdissected human breast cancers. Clinical Proteomics, 6, 129-151. https://doi.org/10.1007/s12014-010-9055-y.
Hutchinson, J. A., Shanware, N. P., Chang, H., & Tibbetts, R. S. (2011). Regulation of ribosomal protein S6 phosphorylation by casein kinase 1 and protein phosphatase 1. Journal of Biological Chemistry, 286, 8688-8696. https://doi.org/10.1074/jbc.M110.141754.
Iwanami, A., Cloughesy, T. F., & Mischel, P. S. (2009). Striking the balance between PTEN and PDK1: It all depends on the cell context. Genes & Development, 23, 1699-1704. https://doi.org/10.1101/gad.1832909.
Jensen, C. J., Buch, M. B., Krag, T. O., Hemmings, B. A., Gammeltoft, S., & Frodin, M. (1999). 90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1. Journal of Biological Chemistry, 274, 27168-27176. https://doi.org/10.1074/jbc.274.38.27168.
Jiang, T., Wang, G., Liu, Y., Feng, L., Wang, M., Liu, J., Chen, Y., & Ouyang, L. (2020). Development of small-molecule tropomyosin receptor kinase (TRK) inhibitors for NTRK fusion cancers. Acta Pharmaceutica Sinica B, 11(2), 355-372. https://doi.org/10.1016/j.apsb.2020.05.004.
Jimenez-Mateos, E. M., Bray, I., Sanz-Rodriguez, A., Engel, T., McKiernan, R. C., Mouri, G., Tanaka, K., Sano, T., Saugstad, J. A., Simon, R. P., Stallings, R. L., & Henshall, D. C. (2011). miRNA Expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132. American Journal of Pathology, 179, 2519-2532. https://doi.org/10.1016/j.ajpath.2011.07.036.
Jimenez-Mateos, E. M., Engel, T., Merino-Serrais, P., McKiernan, R. C., Tanaka, K., Mouri, G., Sano, T., O'Tuathaigh, C., Waddington, J. L., Prenter, S., Delanty, N., Farrell, M. A., O'Brien, D. F., Conroy, R. M., Stallings, R. L., DeFelipe, J., & Henshall, D. C. (2012). Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects. Nature Medicine, 18, 1087-1094. https://doi.org/10.1038/nm.2834.
Jones, R. G., Plas, D. R., Kubek, S., Buzzai, M., Mu, J., Xu, Y., Birnbaum, M. J., & Thompson, C. B. (2005). AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Molecular Cell, 18, 283-293. https://doi.org/10.1016/j.molcel.2005.03.027.
Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005). AMP-activated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolism. Cell Metabolism, 1, 15-25. https://doi.org/10.1016/j.cmet.2004.12.003.
Kalogeris, T., Baines, C. P., Krenz, M., & Korthuis, R. J. (2012). Cell biology of ischemia/reperfusion injury. International Review of Cell and Molecular Biology, 298, 229-317.
Karagkouni, D., Paraskevopoulou, M. D., Chatzopoulos, S., Vlachos, I. S., Tastsoglou, S., Kanellos, I., Papadimitriou, D., Kavakiotis, I., Maniou, S., Skoufos, G., Vergoulis, T., Dalamagas, T., & Hatzigeorgiou, A. G. (2018). DIANA-TarBase v8: A decade-long collection of experimentally supported miRNA-gene interactions. Nucleic Acids Research, 46, D239-D245. https://doi.org/10.1093/nar/gkx1141.
Khoshnam, S. E., Winlow, W., Farbood, Y., Moghaddam, H. F., & Farzaneh, M. (2017). Emerging roles of microRNAs in ischemic stroke: As possible therapeutic agents. Journal of Stroke, 19, 166-187. https://doi.org/10.5853/jos.2016.01368.
Kim, J.-I., Lee, H.-R., Sim , S., Baek , J., Yu , N. K., Choi , J.-H., Ko , H.-G., Lee , Y.-S., Park , S.-W., Kwak , C., Ahn , S.-J., Choi , S. Y., Kim , H., Kim , K.-H., Backx , P. H., Bradley , C. A., Kim , E., Jang , D.-J., Lee , K., … Kaang , B.-K. (2011). PI3Kγ is required for NMDA receptor-dependent long-term depression and behavioral flexibility. Nature Neuroscience, 14, 1447-1454. http://dx.doi.org/10.1038/nn.2937.
Koh, P. O. (2013). Ferulic acid attenuates focal cerebral ischemia-induced decreases in p70S6 kinase and S6 phosphorylation. Neuroscience Letters, 555, 7-11. https://doi.org/10.1016/j.neulet.2013.09.001.
Kozomara, A., Birgaoanu, M., & Griffiths-Jones, S. (2019). miRBase: From microRNA sequences to function. Nucleic Acids Research, 47, D155-D162. https://doi.org/10.1093/nar/gky1141.
Lai, T. W., Zhang, S., & Wang, Y. T. (2014). Excitotoxicity and stroke: Identifying novel targets for neuroprotection. Progress in Neurobiology, 115, 157-188. https://doi.org/10.1016/j.pneurobio.2013.11.006.
Lee, S.-T., Chu, K., Jung, K.-H., Yoon, H.-J., Jeon, D., Kang, K.-M., Park, K.-H., Bae, E.-K., Kim, M., Lee, S. K., & Roh, J.-K. (2010). MicroRNAs induced during ischemic preconditioning. Stroke, 41, 1646-1651. https://doi.org/10.1161/STROKEAHA.110.579649.
Lehman, J. A., & Gomez-Cambronero, J. (2002). Molecular crosstalk between p70S6k and MAPK cell signaling pathways. Biochemical and Biophysical Research Communications, 293, 463-469. https://doi.org/10.1016/S0006-291X(02)00238-3.
Li, J., & McCullough, L. D. (2010). Effects of AMP-activated protein kinase in cerebral ischemia. Journal of Cerebral Blood Flow and Metabolism, 30, 480-492. https://doi.org/10.1038/jcbfm.2009.255.
Li, Y., Yang, C., Zhang, L., & Yang, P. (2017). MicroRNA-210 induces endothelial cell apoptosis by directly targeting PDK1 in the setting of atherosclerosis. Cellular & Molecular Biology Letters, 22, 3. https://doi.org/10.1186/s11658-017-0033-5.
Liou, A. K. F., Clark, R. S., Henshall, D. C., Yin, X. M., & Chen, J. (2003). To die or not to die for neurons in ischemia, traumatic brain injury and epilepsy: A review on the stress-activated signaling pathways and apoptotic pathways. Progress in Neurobiology, 69, 103-142. https://doi.org/10.1016/S0301-0082(03)00005-4.
Lu, W. J., Liang, H. B., Li, Y. F., Tu, X. Q., He, J. R., Ding, K. Q., Yang, G. Y., Xin, X. Y., & Zeng, L. L. (2019). MicroRNA-210-3p targets RGMA to enhance the angiogenic functions of endothelial progenitor cells under hypoxic conditions. Frontiers in Cellular Neuroscience, 13, 223. https://doi.org/10.3389/fncel.2019.00223.
Maas, M. B., & Furie, K. L. (2009). Molecular biomarkers in stroke diagnosis and prognosis. Biomarkers in Medicine, 3, 363-383. https://doi.org/10.2217/bmm.09.30.
Majid, A. (2014). Neuroprotection in stroke: Past, present, and future. ISRN Neurology, 2014, 515716. https://doi.org/10.1155/2014/515716.
Marathe, S., Liu, S., Brai, E., Kaczarowski, M., & Alberi, L. (2015). Notch signaling in response to excitotoxicity induces neurodegeneration via erroneous cell cycle reentry. Cell Death and Differentiation, 22, 1775-1784. https://doi.org/10.1038/cdd.2015.23.
Marsin, A. S., Bouzin, C., Bertrand, L., & Hue, L. (2002). The stimulation of glycolysis by hypoxia in activated monocytes is mediated by AMP-activated protein kinase and inducible 6-phosphofructo-2-kinase. Journal of Biological Chemistry, 277, 30778-30783. https://doi.org/10.1074/jbc.M205213200.
McCullough, L. D., Zeng, Z., Li, H., Landree, L. E., McFadden, J., & Ronnett, G. V. (2005). Pharmacological inhibition of AMP-activated protein kinase provides neuroprotection in stroke. Journal of Biological Chemistry, 280, 20493-20502. https://doi.org/10.1074/jbc.M409985200.
Molloy, N. H., Read, D. E., & Gorman, A. M. (2011). Nerve growth factor in cancer cell death and survival. Cancers (Basel), 3, 510-530. https://doi.org/10.3390/cancers3010510.
Mora, A., Komander, D., van Aalten, D. M., & Alessi, D. R. (2004). PDK1, the master regulator of AGC kinase signal transduction. Seminars in Cell & Developmental Biology, 15, 161-170. https://doi.org/10.1016/j.semcdb.2003.12.022.
Pasculli, B., Barbano, R., Rendina, M., Fontana, A., Copetti, M., Mazza, T., Valori, V. M., Morritti, M., Maiello, E., Graziano, P., Murgo, R., Fazio, V. M., Esteller, M., & Parrella, P. (2019). Hsa-miR-210-3p expression in breast cancer and its putative association with worse outcome in patients treated with Docetaxel. Scientific Reports, 9, 14913. https://doi.org/10.1038/s41598-019-51581-3.
Pfeiffer, S., Anilkumar, U., Chen, G., Ramirez-Peinado, S., Galindo-Moreno, J., Munoz-Pinedo, C., & Prehn, J. H. (2014). Analysis of BH3-only proteins upregulated in response to oxygen/glucose deprivation in cortical neurons identifies Bmf but not Noxa as potential mediator of neuronal injury. Cell Death & Disease, 5, e1456. https://doi.org/10.1038/cddis.2014.426.
Pfeiffer, S., Halang, H., Düssmann, H., Byrne, M. M., & Prehn, J. H. M. (2015). BH3-Only Protein Bmf is required for the maintenance of glucose homeostasis in an in vivo model of HNF1α-MODY diabetes. Cell Death Discovery, 1, 15041. https://doi.org/10.1038/cddiscovery.2015.41.
Plesnila, N., Zhu, C., Culmsee, C., Groger, M., Moskowitz, M. A., & Blomgren, K. (2004). Nuclear translocation of apoptosis-inducing factor after focal cerebral ischemia. Journal of Cerebral Blood Flow and Metabolism, 24, 458-466. https://doi.org/10.1097/00004647-200404000-00011.
Plesnila, N., Zinkel, S., Le, D. A., Amin-Hanjani, S., Wu, Y., Qiu, J., Chiarugi, A., Thomas, S. S., Kohane, D. S., Korsmeyer, S. J., & Moskowitz, M. A. (2001). BID mediates neuronal cell death after oxygen/ glucose deprivation and focal cerebral ischemia. Proceedings of the National Academy of Sciences, 98, 15318-15323. https://doi.org/10.1073/pnas.261323298.
Preibisch, S., Saalfeld, S., & Tomancak, P. (2009). Globally optimal stitching of tiled 3D microscopic image acquisitions. Bioinformatics, 25, 1463-1465. https://doi.org/10.1093/bioinformatics/btp184.
Ren, C. X., Leng, R. X., Fan, Y. G., Pan, H. F., Wu, C. H., & Ye, D. Q. (2016). MicroRNA-210 and its theranostic potential. Expert Opinion on Therapeutic Targets, 20, 1325-1338. https://doi.org/10.1080/14728222.2016.1206890.
Roux, P. P., Shahbazian, D., Vu, H., Holz, M. K., Cohen, M. S., Taunton, J., Sonenberg, N., & Blenis, J. (2007). RAS/ERK signaling promotes site-specific ribosomal protein S6 phosphorylation via RSK and stimulates cap-dependent translation. Journal of Biological Chemistry, 282, 14056-14064. https://doi.org/10.1074/jbc.M700906200.
Rytter, A., Cronberg, T., Asztely, F., Nemali, S., & Wieloch, T. (2003). Mouse hippocampal organotypic tissue cultures exposed to in vitro "ischemia" show selective and delayed CA1 damage that is aggravated by glucose. Journal of Cerebral Blood Flow and Metabolism, 23, 23-33.
Saito, N., Hirai, N., Aoki, K., Suzuki, R., Fujita, S., Nakayama, H., Hayashi, M., Ito, K., Sakurai, T., & Iwabuchi, S. (2019). The oncogene addiction switch from NOTCH to PI3K requires simultaneous targeting of NOTCH and PI3K pathway inhibition in Glioblastoma. Cancers, 11, 121. https://doi.org/10.3390/cancers11010121.
Sharp, F. R., Jickling, G. C., Stamova, B., Tian, Y., Zhan, X., Liu, D., Kuczynski, B., Cox, C. D., & Ander, B. P. (2011). Molecular markers and mechanisms of stroke: RNA studies of blood in animals and humans. Journal of Cerebral Blood Flow and Metabolism, 31, 1513-1531. https://doi.org/10.1038/jcbfm.2011.45.
Steelman, L. S., Chappell, W. H., Abrams, S. L., Kempf, C. R., Long, J., Laidler, P., Mijatovic, S., Maksimovic-Ivanic, D., Stivala, F., Mazzarino, M. C., Donia, M., Fagone, P., Malaponte, G., Nicoletti, F., Libra, M., Milella, M., Tafuri, A., Bonati, A., Bäsecke, J., … McCubrey, J. A. (2011). Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. Aging (Albany NY), 3, 192-222. https://doi.org/10.18632/aging.100296.
Sun, Y., Luo, Z. M., Guo, X. M., Su, D. F., & Liu, X. (2015). An updated role of microRNA-124 in central nervous system disorders: A review. Frontiers in Cellular Neuroscience, 9, 193. https://doi.org/10.3389/fncel.2015.00193.
Team, R. C (2018). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria Available online at https://www.R-project.org/.
Templeton, D. J. (2001). Protein kinases: Getting NEKed for S6K activation. Current Biology, 11, R596-599. https://doi.org/10.1016/S0960-9822(01)00361-X.
Tokar, T., Pastrello, C., Rossos, A. E. M., Abovsky, M., Hauschild, A. C., Tsay, M., Lu, R., & Jurisica, I. (2018). mirDIP 4.1-integrative database of human microRNA target predictions. Nucleic Acids Research, 46, D360-D370.
van Rooij, E., Sutherland, L. B., Qi, X., Richardson, J. A., Hill, J., & Olson, E. N. (2007). Control of stress-dependent cardiac growth and gene expression by a microRNA. Science, 316, 575-579. https://doi.org/10.1126/science.1139089.
Vanhaesebroeck, B., Stephens, L., & Hawkins, P. (2012). PI3K signalling: The path to discovery and understanding. Nature Reviews Molecular Cell Biology, 13, 195-203. https://doi.org/10.1038/nrm3290.
Venna, V. R., Li, J., Benashski, S. E., Tarabishy, S., & McCullough, L. D. (2012). Preconditioning induces sustained neuroprotection by downregulation of adenosine 5'-monophosphate-activated protein kinase. Neuroscience, 201, 280-287. https://doi.org/10.1016/j.neuroscience.2011.11.014.
Vijayan, M., & Reddy, P. H. (2016). Peripheral biomarkers of stroke: Focus on circulatory microRNAs. Biochimica Et Biophysica Acta, 1862, 1984-1993. https://doi.org/10.1016/j.bbadis.2016.08.003.
Vuokila, N., Das Gupta, S., Huusko, R., Tohka, J., Puhakka, N., & Pitkanen, A. (2020). Elevated acute plasma miR-124-3p level relates to evolution of larger cortical lesion area after traumatic brain injury. Neuroscience, 433, 21-35. https://doi.org/10.1016/j.neuroscience.2020.02.045.
Weisova, P., Concannon, C. G., Devocelle, M., Prehn, J. H., & Ward, M. W. (2009). Regulation of glucose transporter 3 surface expression by the AMP-activated protein kinase mediates tolerance to glutamate excitation in neurons. Journal of Neuroscience, 29, 2997-3008. https://doi.org/10.1523/JNEUROSCI.0354-09.2009.
Weisova, P., Davila, D., Tuffy, L. P., Ward, M. W., Concannon, C. G., & Prehn, J. H. (2011). Role of 5'-adenosine monophosphate-activated protein kinase in cell survival and death responses in neurons. Antioxidants & Redox Signaling, 14, 1863-1876. https://doi.org/10.1089/ars.2010.3544.
Weng, H., Shen, C., Hirokawa, G., Ji, X., Takahashi, R., Shimada, K., Kishimoto, C., & Iwai, N. (2011). Plasma miR-124 as a biomarker for cerebral infarction. Biomedical Research, 32, 135-141. https://doi.org/10.2220/biomedres.32.135.
Wickham, H. (2011). The split-apply-combine strategy for data analysis. Journal of Statistical Software, 40, 1-29. https://doi.org/10.18637/jss.v040.i01.
Wilczynska, A., & Bushell, M. (2015). The complexity of miRNA-mediated repression. Cell Death and Differentiation, 22, 22-33. https://doi.org/10.1038/cdd.2014.112.
Williams, M. R., Arthur, J. S., Balendran, A., van der Kaay, J., Poli, V., Cohen, P., & Alessi, D. R. (2000). The role of 3-phosphoinositide-dependent protein kinase 1 in activating AGC kinases defined in embryonic stem cells. Current Biology, 10, 439-448. https://doi.org/10.1016/S0960-9822(00)00441-3.
Wu, S. B., & Wei, Y. H. (2012). AMPK-mediated increase of glycolysis as an adaptive response to oxidative stress in human cells: Implication of the cell survival in mitochondrial diseases. Biochimica Et Biophysica Acta, 1822, 233-247. https://doi.org/10.1016/j.bbadis.2011.09.014.
Yu, G., & He, Q. Y. (2016). ReactomePA: An R/Bioconductor package for reactome pathway analysis and visualization. Molecular BioSystems, 12, 477-479. https://doi.org/10.1039/C5MB00663E.
Yu, G., Wang, L. G., Han, Y., & He, Q. Y. (2012). clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS: A Journal of Integrative Biology, 16, 284-287. https://doi.org/10.1089/omi.2011.0118.
Zeng, L., Liu, J., Wang, Y., Wang, L., Weng, S., Tang, Y., Zheng, C., Cheng, Q., Chen, S., & Yang, G. Y. et al (2011). MicroRNA-210 as a novel blood biomarker in acute cerebral ischemia. Frontiers in Bioscience (Elite Ed), 3, 1265-1272.
Zhang, R., Guo, Y., Ma, Z., Ma, G., Xue, Q., Li, F., & Liu, L. (2017). Long non-coding RNA PTENP1 functions as a ceRNA to modulate PTEN level by decoying miR-106b and miR-93 in gastric cancer. Oncotarget, 8, 26079-26089. https://doi.org/10.18632/oncotarget.15317.