Inhibition of Protein Kinase R by C16 Protects the Retinal Ganglion Cells from Hypoxia-induced Oxidative Stress, Inflammation, and Apoptosis

References

• Kaur C, Foulds WS, Ling E-A. Hypoxia-ischemia and retinal ganglion cell damage. Clin Ophthalmol. 2008;2(4):879. doi:10.2147/OPTH.S3361.
   PubMedGoogle Scholar
• Kaur C, Sivakumar V, Robinson R, Foulds WS, Luu CD, Ling EA. Neuroprotective effect of melatonin against hypoxia‐induced retinal ganglion cell death in neonatal rats. J Pineal Res. 2013;54(2):190–206. doi:10.1111/jpi.12016.
   PubMed Web of Science ®Google Scholar
• Nakayama M, Aihara M, Chen Y-N, Araie M, Tomita-Yokotani K, Iwashina T. Neuroprotective effects of flavonoids on hypoxia-, glutamate-, and oxidative stress-induced retinal ganglion cell death. Mol Vis. 2011;17:1784.
   PubMed Web of Science ®Google Scholar
• Kaur C, Rathnasamy G, Foulds W, Ling E. Cellular and molecular mechanisms of retinal ganglion cell death in hypoxic-ischemic injuries. J Neurol Exp Neurosci. 2015;1:10–19.
   Google Scholar
• Fu P, Wu Q, Hu J, Li T, Gao F. Baclofen protects primary rat retinal ganglion cells from chemical hypoxia-induced apoptosis through the Akt and PERK pathways. Front Cell Neurosci. 2016;10:255. doi:10.3389/fncel.2016.00255.
   PubMed Web of Science ®Google Scholar
• Khatib T, Martin K. Protecting retinal ganglion cells. Eye. 2017;31(2):218–24. doi:10.1038/eye.2016.299.
   PubMed Web of Science ®Google Scholar
• Garcia-Ortega M, Lopez G, Jimenez G, Garcia-Garcia J, Conde V, Boulaiz H, Carrillo E, Perán M, Marchal J, Garcia M. Clinical and therapeutic potential of protein kinase PKR in cancer and metabolism. Expert Rev Mol Med. 2017;19:e9.
   PubMed Web of Science ®Google Scholar
• Gal-Ben-Ari S, Barrera I, Ehrlich M, Rosenblum K. PKR: a kinase to remember. Front Mol Neurosci. 2019;11:480. doi:10.3389/fnmol.2018.00480.
   PubMed Web of Science ®Google Scholar
• Alirezaei M, Watry DD, Flynn CF, Kiosses WB, Masliah E, Williams BR, Kaul M, Lipton SA, Fox HS. Human immunodeficiency virus-1/surface glycoprotein 120 induces apoptosis through RNA-activated protein kinase signaling in neurons. J Neurosci. 2007;27(41):11047–55. doi:10.1523/JNEUROSCI.2733-07.2007.
   PubMed Web of Science ®Google Scholar
• Shimazawa M, Ito Y, Inokuchi Y, Hara H. Involvement of double-stranded RNA-dependent protein kinase in ER stress-induced retinal neuron damage. Invest Ophthalmol Vis Sci. 2007;48(8):3729–36. doi:10.1167/iovs.06-1122.
   PubMed Web of Science ®Google Scholar
• Couturier J, Page G, Morel M, Gontier C, Lecron J-C, Pontcharraud R, Fauconneau B, Paccalin M. Inhibition of double-stranded RNA-dependent protein kinase strongly decreases cytokine production and release in peripheral blood mononuclear cells from patients with Alzheimer’s disease. J Alzheimers Dis. 2010;21(4):1217–31. doi:10.3233/JAD-2010-100258.
   PubMed Web of Science ®Google Scholar
• Hugon J, Mouton-Liger F, Dumurgier J, Paquet C. PKR involvement in Alzheimer’s disease. Alzheimers Res Ther. 2017;9:83.
   PubMedGoogle Scholar
• Lourenco MV, Clarke JR, Frozza RL, Bomfim TR, Forny-Germano L, Batista AF, Sathler LB, Brito-Moreira J, Amaral OB, Silva CATNF-Α. mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer’s β-amyloid oligomers in mice and monkeys. Cell Metab. 2013;18(6):831–43. doi:10.1016/j.cmet.2013.11.002.
   PubMed Web of Science ®Google Scholar
• Jiang Y, Steinle JJ. Epac1 inhibits PKR to reduce NLRP3 inflammasome proteins in retinal endothelial cells. J Inflamm Res. 2019;12:153. doi:10.2147/JIR.S210441.
   PubMed Web of Science ®Google Scholar
• Chang RCC, Suen KC, Ma CH, Elyaman W, Ng HK, Hugon J. Involvement of double‐stranded RNA‐dependent protein kinase and phosphorylation of eukaryotic initiation factor‐2α in neuronal degeneration. J Neurochem. 2002;83(5):1215–25. doi:10.1046/j.1471-4159.2002.01237.x.
   PubMed Web of Science ®Google Scholar
• Peel AL, Rao RV, Cottrell BA, Hayden MR, Ellerby LM, Bredesen DE. Double-stranded RNA-dependent protein kinase, PKR, binds preferentially to Huntington’s disease (HD) transcripts and is activated in HD tissue. Hum Mol Genet. 2001;10(15):1531–38. doi:10.1093/hmg/10.15.1531.
   PubMed Web of Science ®Google Scholar
• Xiao J, Tan Y, Li Y, Luo Y. The specific protein kinase R (PKR) inhibitor C16 protects neonatal hypoxia-ischemia brain damages by inhibiting neuroinflammation in a neonatal rat model. Med Sci Monit. 2016;22:5074. doi:10.12659/MSM.898139.
   PubMed Web of Science ®Google Scholar
• Hugon J, Paquet C, Chang R-C-C. Could PKR inhibition modulate human neurodegeneration? Expert Rev Neurother. 2009;9(10):1455–57. doi:10.1586/ern.09.92.
   PubMed Web of Science ®Google Scholar
• Zhu M, Liu X, Wang S, Miao J, Wu L, Yang X, Wang Y, Kang L, Li W, Cui C. PKR promotes choroidal neovascularization via upregulating the PI3K/Akt signaling pathway in VEGF expression. Mol Vis. 2016;22:1361.
   PubMed Web of Science ®Google Scholar
• Otori Y, Kusaka S, Kawasaki A, Morimura H, Miki A, Tano Y. Protective effect of nilvadipine against glutamate neurotoxicity in purified retinal ganglion cells. Brain Res. 2003;961(2):213–19. doi:10.1016/S0006-8993(02)03951-3.
   PubMed Web of Science ®Google Scholar
• Tulsawani R, Kelly LS, Fatma N, Chhunchha B, Kubo E, Kumar A, Singh DP. Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage. BMC Neurosci. 2010;11(1):125. doi:10.1186/1471-2202-11-125.
   PubMedGoogle Scholar
• Harris AL. Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer. 2002;2(1):38–47. doi:10.1038/nrc704.
   PubMed Web of Science ®Google Scholar
• Büchi ER. Cell death in the rat retina after a pressure-induced ischemia-reperfusion insult: an electron microscopic study. I. ganglion cell layer and inner nuclear layer. Exp Eye Res. 1992;55(4):605–13. doi:10.1016/S0014-4835(05)80173-3.
   PubMed Web of Science ®Google Scholar
• Joo C-K, Choi J-S, Ko HW, Park KY, Sohn S, Chun MH, Oh YJ, Gwag BJ. Necrosis and apoptosis after retinal ischemia: involvement of NMDA-mediated excitotoxicity and p53. Invest Ophthalmol Vis Sci. 1999;40:713–20.
   PubMed Web of Science ®Google Scholar
• Klemm P, Hurst J, Dias Blak M, Herrmann T, Melchinger M, Bartz‐Schmidt KU, Zeck G, Schultheiss M, Spitzer MS, Schnichels S. Hypothermia protects retinal ganglion cells against hypoxia‐induced cell death in a retina organ culture model. Clin Experiment Ophthalmol. 2019;47(8):1043–54. doi:10.1111/ceo.13565.
   PubMed Web of Science ®Google Scholar
• Inman DM, Lambert WS, Calkins DJ, Horner PJ. α-Lipoic acid antioxidant treatment limits glaucoma-related retinal ganglion cell death and dysfunction. PLoS ONE. 2013;8(6):e65389. doi:10.1371/journal.pone.0065389.
   PubMed Web of Science ®Google Scholar
• Payne AJ, Kaja S, Naumchuk Y, Kunjukunju N, Koulen P. Antioxidant drug therapy approaches for neuroprotection in chronic diseases of the retina. Int J Mol Sci. 2014;15(2):1865–86. doi:10.3390/ijms15021865.
   PubMed Web of Science ®Google Scholar
• Rohowetz LJ, Kraus JG, Koulen P. Reactive oxygen species-mediated damage of retinal neurons: drug development targets for therapies of chronic neurodegeneration of the retina. Int J Mol Sci. 2018;19(11):3362. doi:10.3390/ijms19113362.
   PubMed Web of Science ®Google Scholar
• Zhang Z, Qin X, Zhao X, Tong N, Gong Y, Zhang W, Wu X. Valproic acid regulates antioxidant enzymes and prevents ischemia/reperfusion injury in the rat retina. Curr Eye Res. 2012;37(5):429–37. doi:10.3109/02713683.2011.653616.
   PubMed Web of Science ®Google Scholar
• Szabo ME, Droy-Lefaix MT, Doly M, Braquet P. Free radical-mediated effects in reperfusion injury: a histologic study with superoxide dismutase and EGB 761 in rat retina. Ophthalmic Res. 1991;23(4):225–34. doi:10.1159/000267107.
   PubMed Web of Science ®Google Scholar
• Charles I, Khalyfa A, Kumar DM, Krishnamoorthy RR, Roque RS, Cooper N, Agarwal N. Serum deprivation induces apoptotic cell death of transformed rat retinal ganglion cells via mitochondrial signaling pathways. Invest Ophthalmol Vis Sci. 2005;46(4):1330–38. doi:10.1167/iovs.04-0363.
   PubMed Web of Science ®Google Scholar
• Sivakumar V, Foulds WS, Luu CD, Ling EA, Kaur C. Retinal ganglion cell death is induced by microglia derived pro‐inflammatory cytokines in the hypoxic neonatal retina. J Pathol. 2011;224(2):245–60. doi:10.1002/path.2858.
   PubMed Web of Science ®Google Scholar
• Hong S, Lee JE, Kim CY, Seong GJ. Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line. BMC Neurosci. 2007;8(1):81. doi:10.1186/1471-2202-8-81.
   PubMedGoogle Scholar
• Produit-Zengaffinen N, Favez T, Pournaras CJ, Schorderet DF. JNK inhibition reduced retinal ganglion cell death after ischemia/reperfusion in vivo and after hypoxia in vitro. Retin Degener Dis. 2016;854:677–83.
   Google Scholar
• Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, Green DR. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science. 2004;303(5660):1010–14. doi:10.1126/science.1092734.
   PubMed Web of Science ®Google Scholar
• Deng Y, Ren X, Yang L, Lin Y, Wu X. A JNK-dependent pathway is required for TNFα-induced apoptosis. Cell. 2003;115(1):61–70. doi:10.1016/S0092-8674(03)00757-8.
   PubMed Web of Science ®Google Scholar
• Dhanasekaran DN, Reddy EP. JNK signaling in apoptosis. Oncogene. 2008;27(48):6245–51. doi:10.1038/onc.2008.301.
   PubMed Web of Science ®Google Scholar
• Cai B, Chang SH, Becker EB, Bonni A, Xia Z. p38 MAP kinase mediates apoptosis through phosphorylation of BimEL at Ser-65. J Biol Chem. 2006;281(35):25215–22. doi:10.1074/jbc.M512627200.
   PubMed Web of Science ®Google Scholar
• Plotnikov A, Zehorai E, Procaccia S, The SR. MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation. Biochim Biophys Acta. 2011;1813(9):1619–33. doi:10.1016/j.bbamcr.2010.12.012.
   PubMed Web of Science ®Google Scholar
• Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev. 2011;75:50–83.
   PubMed Web of Science ®Google Scholar
• Zhang H-K, Ye Y, Li K-J, Zhao Z-N, He J-F. Gypenosides prevent H 2 O 2-induced retinal ganglion cell apoptosis by concurrently suppressing the neuronal oxidative stress and inflammatory response. J Mol Neurosci. 2020;1–13. doi:10.1007/s12031-019-01393-x.
   PubMed Web of Science ®Google Scholar
• Gao F-J, Zhang S-H, Xu P, Yang B-Q, Zhang R, Cheng Y, Zhou X-J, Huang W-J, Wang M, Chen J-Y. Quercetin declines apoptosis ameliorates mitochondrial function and improves retinal ganglion cell survival and function in in vivo model of glaucoma in rat and retinal ganglion cell culture in vitro. Front Mol Neurosci. 2017;10:285. doi:10.3389/fnmol.2017.00285.
   PubMed Web of Science ®Google Scholar
• Li C-P, Qiu G-Z, Liu B, Chen J-L, Fu H-T. Neuroprotective effect of lignans extracted from eucommia ulmoides olivon glaucoma-related neurodegeneration. Neurol Sci. 2016;37(5):755–62. doi:10.1007/s10072-016-2491-3.
   PubMed Web of Science ®Google Scholar
• Lv B, Chen T, Xu Z, Huo F, Wei Y, Yang X. Crocin protects retinal ganglion cells against H2O2-induced damage through the mitochondrial pathway and activation of NF-κB. Int J Mol Med. 2016;37(1):225–32. doi:10.3892/ijmm.2015.2418.
   PubMed Web of Science ®Google Scholar
• Qi X, Sun L, Lewin AS, Hauswirth WW, Guy J. Long-term suppression of neurodegeneration in chronic experimental optic neuritis: antioxidant gene therapy. Invest Ophthalmol Vis Sci. 2007;48(12):5360–70. doi:10.1167/iovs.07-0254.
   PubMed Web of Science ®Google Scholar
• Tezel Gln YX. Caspase-independent component of retinal ganglion cell death, in vitro. Invest Ophthalmol Vis Sci. 2004;45:4049–59.
   PubMed Web of Science ®Google Scholar
• Bando Y, Onuki R, Katayama T, Manabe T, Kudo T, Taira K, Tohyama M. Double-strand RNA dependent protein kinase (PKR) is involved in the extrastriatal degeneration in Parkinson’s disease and Huntington’s disease. Neurochem Int. 2005;46(1):11–18. doi:10.1016/j.neuint.2004.07.005.
   PubMed Web of Science ®Google Scholar
• Page G, Bilan AR, Ingrand S, Lafay-Chebassier C, Pain S, Pochat MP, Bouras C, Bayer T, Hugon J. Activated double-stranded RNA-dependent protein kinase and neuronal death in models of Alzheimer’s disease. Neuroscience. 2006;139(4):1343–54. doi:10.1016/j.neuroscience.2006.01.047.
   PubMed Web of Science ®Google Scholar
• Peel AL, Bredesen DE. Activation of the cell stress kinase PKR in Alzheimer’s disease and human amyloid precursor protein transgenic mice. Neurobiol Dis. 2003;14(1):52–62. doi:10.1016/S0969-9961(03)00086-X.
   PubMed Web of Science ®Google Scholar
• Lucia K, Wu Y, Garcia JM, Barlier A, Buchfelder M, Saeger W, Renner U, Stalla GK, Theodoropoulou M. Hypoxia and the hypoxia-inducible factor 1α activate protein kinase A by repressing RII beta subunit transcription. Oncogene. 2020;39(16):3367–80. doi:10.1038/s41388-020-1223-6.
   PubMed Web of Science ®Google Scholar
• Watanabe T, Imamura T, Hiasa Y. Roles of protein kinase R in cancer: potential as a therapeutic target. Cancer Sci. 2018;109(4):919–25. doi:10.1111/cas.13551.
   PubMed Web of Science ®Google Scholar
• Gil J, Garcı́a MA, Caspase EM. 9 activation by the dsRNA-dependent protein kinase, PKR: molecular mechanism and relevance. FEBS Lett. 2002;529(2–3):249–55. doi:10.1016/S0014-5793(02)03348-3.
   PubMed Web of Science ®Google Scholar
• Gil J, García MA, Gomez-Puertas P, Guerra S, Rullas J, Nakano H, Alcamí J, Esteban M. TRAF family proteins link PKR with NF-κB activation. Mol Cell Biol. 2004;24(10):4502–12. doi:10.1128/MCB.24.10.4502-4512.2004.
   PubMed Web of Science ®Google Scholar
• Lu B, Nakamura T, Inouye K, Li J, Tang Y, Lundbäck P, Valdes-Ferrer SI, Olofsson PS, Kalb T, Roth J. Novel role of PKR in inflammasome activation and HMGB1 release. Nature. 2012;488(7413):670–74. doi:10.1038/nature11290.
   PubMed Web of Science ®Google Scholar
• Dedoni S, Olianas MC, Onali P. Interferon‐β induces apoptosis in human SH‐SY5Y neuroblastoma cells through activation of JAK–STAT signaling and down‐regulation of PI3K/Akt pathway. J Neurochem. 2010;115(6):1421–33. doi:10.1111/j.1471-4159.2010.07046.x.
   PubMedGoogle Scholar
• Jammi NV, Whitby LR, Beal PA. Small molecule inhibitors of the RNA-dependent protein kinase. Biochem Biophys Res Commun. 2003;308(1):50–57. doi:10.1016/S0006-291X(03)01318-4.
   PubMed Web of Science ®Google Scholar
• Tronel C, Page G, Bodard S, Chalon S, Antier D. The specific PKR inhibitor C16 prevents apoptosis and IL-1β production in an acute excitotoxic rat model with a neuroinflammatory component. Neurochem Int. 2014;64:73–83. doi:10.1016/j.neuint.2013.10.012.
   PubMed Web of Science ®Google Scholar