Thrombolysis by PLAT/tPA increases serum free IGF1 leading to a decrease of deleterious autophagy following brain ischemia

References

• Feigin VL, Nichols E, Alam T. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the global burden of disease study 2016. Lancet Neurol. 2019;18:459–480.
   PubMed Web of Science ®Google Scholar
• Thiebaut AM, Gauberti M, Ali C, et al. The role of plasminogen activators in stroke treatment: fibrinolysis and beyond. Lancet Neurol. 2018;17:1121–1132.
   PubMed Web of Science ®Google Scholar
• Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372:11–20.
   PubMed Web of Science ®Google Scholar
• Tissue plasminogen activator for acute ischemic stroke. The national institute of neurological disorders and stroke rt-PA stroke study group. N Engl J Med. 1995;333:1581–1587.
   PubMed Web of Science ®Google Scholar
• Thiebaut AM, Hedou E, Marciniak SJ, et al. Proteostasis during cerebral Ischemia. Front Neurosci. 2019;13:637.
   PubMed Web of Science ®Google Scholar
• Jung CH, Jun CB, Ro SH, et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell. 2009;20:1992–2003.
   PubMed Web of Science ®Google Scholar
• Louessard M, Bardou I, Lemarchand E, et al. Activation of cell surface GRP78 decreases endoplasmic reticulum stress and neuronal death. Cell Death Differ. 2017;24:1518–1529.
   PubMed Web of Science ®Google Scholar
• Grummisch JA, Jadavji NM, Smith PD. tPA promotes cortical neuron survival via mTOR-dependent mechanisms. Mol Cell Neurosci. 2016;74:25–33.
   PubMed Web of Science ®Google Scholar
• Wu F, Wu J, Nicholson AD, et al. Tissue-type plasminogen activator regulates the neuronal uptake of glucose in the ischemic brain. J Neurosci. 2012;32:9848–9858.
   PubMed Web of Science ®Google Scholar
• Wu F, Echeverry R, Wu J, et al. Tissue-type plasminogen activator protects neurons from excitotoxin-induced cell death via activation of the ERK1/2-CREB-ATF3 signaling pathway. Mol Cell Neurosci. 2013;52:9–19.
   PubMed Web of Science ®Google Scholar
• Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. 2021;1:1–382.
   Web of Science ®Google Scholar
• Ginet V, Spiehlmann A, Rummel C, et al. Involvement of autophagy in hypoxic-excitotoxic neuronal death. Autophagy. 2014;10:846–860.
   PubMed Web of Science ®Google Scholar
• Bhaskar PT, Hay N. The two TORCs and Akt. Dev Cell. 2007;12:487–502.
   PubMed Web of Science ®Google Scholar
• Kim J, Kundu M, Viollet B, et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011;13:132–141.
   PubMed Web of Science ®Google Scholar
• Huang J, Manning BD. A complex interplay between Akt, TSC2 and the two mTOR complexes. Biochem Soc Trans. 2009;37:217–222.
   PubMed Web of Science ®Google Scholar
• Carriere A, Cargnello M, Julien LA, et al. Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated raptor phosphorylation. Curr Biol. 2008;18:1269–1277.
   PubMed Web of Science ®Google Scholar
• Morris EJ, Jha S, Restaino CR, et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov. 2013;3:742–750.
   PubMed Web of Science ®Google Scholar
• Zheng Y, Gu S, Li X, et al. Berbamine postconditioning protects the heart from ischemia/reperfusion injury through modulation of autophagy. Cell Death Dis. 2017;8:e2577.
   PubMed Web of Science ®Google Scholar
• Echeverry R, Wu J, Haile WB, et al. Tissue-type plasminogen activator is a neuroprotectant in the mouse hippocampus. J Clin Invest. 2010;120:1269–1277.
   Web of Science ®Google Scholar
• An J, Zhang C, Polavarapu R, et al. Tissue-type plasminogen activator and the low-density lipoprotein receptor-related protein induce Akt phosphorylation in the ischemic brain. Blood. 2008;112:2787–2794.
   PubMed Web of Science ®Google Scholar
• Liot G, Roussel BD, Lebeurrier N, et al. Tissue-type plasminogen activator rescues neurones from serum deprivation-induced apoptosis through a mechanism independent of its proteolytic activity. J Neurochem. 2006;98:1458–1464.
   PubMed Web of Science ®Google Scholar
• Bertrand T, Lesept F, Chevilley A, et al. Conformations of tissue plasminogen activator (tPA) orchestrate neuronal survival by a crosstalk between EGFR and NMDAR. Cell Death Dis. 2015;6:e1924.
   PubMed Web of Science ®Google Scholar
• Lemarchand E, Maubert E, Haelewyn B, et al. Stressed neurons protect themselves by a tissue-type plasminogen activator-mediated EGFR-dependent mechanism. Cell Death Differ. 2016;23(1):123–31.
   PubMed Web of Science ®Google Scholar
• Parcq J, Bertrand T, Montagne A, et al. Unveiling an exceptional zymogen: the single-chain form of tPA is a selective activator of NMDA receptor-dependent signaling and neurotoxicity. Cell Death Differ. 2012;19:1983–1991.
   PubMed Web of Science ®Google Scholar
• Duan Z, Choy E, Harmon D, et al. Insulin-like growth factor-I receptor tyrosine kinase inhibitor cyclolignan picropodophyllin inhibits proliferation and induces apoptosis in multidrug resistant osteosarcoma cell lines. Mol Cancer Ther. 2009;8:2122–2130.
   PubMed Web of Science ®Google Scholar
• Orset C, Haelewyn B, Allan SM, et al. Efficacy of Alteplase in a mouse model of acute Ischemic stroke: a retrospective pooled analysis. Stroke. 2016;47:1312–1318.
   PubMed Web of Science ®Google Scholar
• Orset C, Macrez R, Young AR, et al. Mouse model of in situ thromboembolic stroke and reperfusion. Stroke. 2007;38:2771–2778.
   PubMed Web of Science ®Google Scholar
• Ballard FJ, Knowles SE, Walton PE, et al. Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I), IGF-II and des(1-3)IGF-I in rats. J Endocrinol. 1991;128:197–204.
   PubMed Web of Science ®Google Scholar
• Forbes K, Souquet B, Garside R, et al. Transforming growth factor-{beta} (TGF{beta}) receptors I/II differentially regulate TGF{beta}1 and IGF-binding protein-3 mitogenic effects in the human placenta. Endocrinology. 2010;151:1723–1731.
   PubMed Web of Science ®Google Scholar
• Gluckman P, Klempt N, Guan J, et al. A role for IGF-1 in the rescue of CNS neurons following hypoxic-ischemic injury. Biochem Biophys Res Commun. 1992;182:593–599.
   PubMed Web of Science ®Google Scholar
• Xu S, Savage P, Burton JL, et al. Proteolysis of insulin-like growth factor-binding protein-3 by human skin keratinocytes in culture in comparison to that in skin interstitial fluid: the role and regulation of components of the plasmin system. J Clin Endocrinol Metab. 1997;82:1863–1868.
   PubMed Web of Science ®Google Scholar
• Guertin DA, Stevens DM, Thoreen CC, et al. Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell. 2006;11:859–871.
   PubMed Web of Science ®Google Scholar
• Jacinto E, Facchinetti V, Liu D, et al. SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell. 2006;127:125–137.
   PubMed Web of Science ®Google Scholar
• Wen YD, Sheng R, Zhang LS, et al. Neuronal injury in rat model of permanent focal cerebral ischemia is associated with activation of autophagic and lysosomal pathways. Autophagy. 2008;4:762–769.
   PubMed Web of Science ®Google Scholar
• Wang N, Yang L, Zhang H, et al. MicroRNA-9a-5p Alleviates ischemia injury after focal cerebral ischemia of the rat by targeting ATG5-mediated autophagy. Cell Physiol Biochem. 2018;45:78–87.
   PubMedGoogle Scholar
• Puyal J, Vaslin A, Mottier V, et al. Postischemic treatment of neonatal cerebral ischemia should target autophagy. Ann Neurol. 2009;66:378–389.
   PubMed Web of Science ®Google Scholar
• Xie C, Ginet V, Sun Y, et al. Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury. Autophagy. 2016;12:410–423.
   PubMed Web of Science ®Google Scholar
• Troncoso R, Vicencio JM, Parra V, et al. Energy-preserving effects of IGF-1 antagonize starvation-induced cardiac autophagy. Cardiovasc Res. 2012;93:320–329.
   PubMed Web of Science ®Google Scholar
• Lin Y, Deng W, Pang J, et al. The microRNA-99 family modulates hepatitis B virus replication by promoting IGF-1R/PI3K/Akt/mTOR/ULK1 signaling-induced autophagy. Cell Microbiol. 2017;19(5).
   Web of Science ®Google Scholar
• Wang S, Gu K. Insulin-like growth factor 1 inhibits autophagy of human colorectal carcinoma drug-resistant cells via the protein kinase B/mammalian target of rapamycin signaling pathway. Mol Med Rep. 2018;17:2952–2956.
   PubMed Web of Science ®Google Scholar
• Kooijman R, Sarre S, Michotte Y, et al. Insulin-like growth factor I: a potential neuroprotective compound for the treatment of acute ischemic stroke? Stroke. 2009;40(4):e83–8.
   PubMed Web of Science ®Google Scholar
• De Geyter D, De Smedt A, Stoop W, et al. Central IGF-I receptors in the brain are instrumental to neuroprotection by systemically injected IGF-I in a rat model for ischemic stroke. CNS Neurosci Ther. 2016;22:611–616.
   PubMed Web of Science ®Google Scholar
• Kelley KM, Oh Y, Gargosky SE, et al. Insulin-like growth factor-binding proteins (IGFBPs) and their regulatory dynamics. Int J Biochem Cell Biol. 1996;28:619–637.
   PubMed Web of Science ®Google Scholar
• Schwab S, Spranger M, Krempien S, et al. Plasma insulin-like growth factor I and IGF binding protein 3 levels in patients with acute cerebral ischemic injury. Stroke. 1997;28(9):1744–1748.
   PubMed Web of Science ®Google Scholar
• Blum WF, Albertsson-Wikland K, Rosberg S, et al. Serum levels of insulin-like growth factor I (IGF-I) and IGF binding protein 3 reflect spontaneous growth hormone secretion. J Clin Endocrinol Metab. 1993;76:1610–1616.
   PubMed Web of Science ®Google Scholar
• Blat C, Villaudy J, Binoux M. In vivo proteolysis of serum insulin-like growth factor (IGF) binding protein-3 results in increased availability of IGF to target cells. J Clin Invest. 1994;93:2286–2290.
   PubMed Web of Science ®Google Scholar
• Imai Y, Moralez A, Andag U, et al. Substitutions for hydrophobic amino acids in the N-terminal domains of IGFBP-3 and −5 markedly reduce IGF-I binding and alter their biologic actions. J Biol Chem. 2000;275:18188–18194.
   PubMed Web of Science ®Google Scholar
• Jogie-Brahim S, Feldman D, Oh Y. Unraveling insulin-like growth factor binding protein-3 actions in human disease. Endocr Rev. 2009;30:417–437.
   PubMed Web of Science ®Google Scholar
• Booth BA, Boes M, Bar RS. IGFBP-3 proteolysis by plasmin, thrombin, serum: heparin binding, IGF binding, and structure of fragments. A J Physiol. 1996;271:E465–70.
   PubMed Web of Science ®Google Scholar
• Fowlkes JL, Enghild JJ, Suzuki K, et al. Matrix metalloproteinases degrade insulin-like growth factor-binding protein-3 in dermal fibroblast cultures. J Biol Chem. 1994;269:25742–25746.
   PubMed Web of Science ®Google Scholar
• Bang P, Fielder PJ. Human pregnancy serum contains at least two distinct proteolytic activities with the ability to degrade insulin-like growth factor binding protein-3. Endocrinology. 1997;138:3912–3917.
   PubMed Web of Science ®Google Scholar
• Pasquet N, Douceau S, Naveau M, et al. Tissue-type plasminogen activator controlled corticogenesis through a mechanism dependent of NMDA receptors expressed on radial glial cells. Cereb Cortex. 2019;29(6):2482–2498.
   Google Scholar
• Nieto-Estevez V, Defterali C, Vicario-Abejon C. IGF-I: a key growth factor that regulates neurogenesis and synaptogenesis from embryonic to adult stages of the brain. Front Neurosci. 2016;10:52.
   PubMed Web of Science ®Google Scholar
• Liu W, D’Ercole JA, Ye P. Blunting type 1 insulin-like growth factor receptor expression exacerbates neuronal apoptosis following hypoxic/ischemic injury. BMC Neurosci. 2011;12:64.
   PubMed Web of Science ®Google Scholar
• Bake S, Selvamani A, Cherry J, et al. Blood brain barrier and neuroinflammation are critical targets of IGF-1-mediated neuroprotection in stroke for middle-aged female rats. PLoS One. 2014;9:e91427.
   PubMed Web of Science ®Google Scholar
• Siao CJ, Fernandez SR, Tsirka SE. Cell type-specific roles for tissue plasminogen activator released by neurons or microglia after excitotoxic injury. J Neurosci. 2003;23:3234–3242.
   PubMed Web of Science ®Google Scholar
• Flavin MP, Zhao G, Ho LT. Microglial tissue plasminogen activator (tPA) triggers neuronal apoptosis in vitro. Glia. 2000;29:347–354.
   PubMed Web of Science ®Google Scholar
• Pu H, Shi Y, Zhang L, et al. Protease-independent action of tissue plasminogen activator in brain plasticity and neurological recovery after ischemic stroke. Proc Natl Acad Sci U S A. 2019;116:9115–9124.
   PubMed Web of Science ®Google Scholar
• Benchenane K, Berezowski V, Ali C, et al. Tissue-type plasminogen activator crosses the intact blood-brain barrier by low-density lipoprotein receptor-related protein-mediated transcytosis. Circulation. 2005;111:2241–2249.
   PubMed Web of Science ®Google Scholar
• Liang M, Woodard LE, Liang A, et al. Protective role of insulin-like growth factor-1 receptor in endothelial cells against unilateral ureteral obstruction-induced renal fibrosis. Am J Pathol. 2015;185:1234–1250.
   PubMed Web of Science ®Google Scholar
• Polavarapu R, Gongora MC, Yi H, et al. Tissue-type plasminogen activator-mediated shedding of astrocytic low-density lipoprotein receptor-related protein increases the permeability of the neurovascular unit. Blood. 2007;109:3270–3278.
   PubMed Web of Science ®Google Scholar
• Roussel BD, Mysiorek C, Rouhiainen A, et al. HMGB-1 promotes fibrinolysis and reduces neurotoxicity mediated by tissue plasminogen activator. J Cell Sci. 2011;124:2070–2076.
   PubMed Web of Science ®Google Scholar
• Grishchuk Y, Ginet V, Truttmann AC, et al. Beclin 1-independent autophagy contributes to apoptosis in cortical neurons. Autophagy. 2011;7:1115–1131.
   PubMed Web of Science ®Google Scholar
• Vaslin A, Puyal J, Borsello T, et al. Excitotoxicity-related endocytosis in cortical neurons. J Neurochem. 2007;102:789–800.
   PubMed Web of Science ®Google Scholar
• Kabeya Y, Mizushima N, Ueno T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000;19:5720–5728.
   PubMed Web of Science ®Google Scholar
• Drouet V, Perrin V, Hassig R, et al. Sustained effects of nonallele-specific Huntingtin silencing. Ann Neurol. 2009;65:276–285.
   PubMed Web of Science ®Google Scholar
• Hottinger AF, Azzouz M, Deglon N, et al. Complete and long-term rescue of lesioned adult motoneurons by lentiviral-mediated expression of glial cell line-derived neurotrophic factor in the facial nucleus. J Neurosci. 2000;20:5587–5593.
   PubMed Web of Science ®Google Scholar