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Effects of unoprostone on phosphorylated extracellular signal-regulated kinase expression in endothelin-1-induced retinal and optic nerve damage

Published online by Cambridge University Press:  28 April 2008

YASUNARI MUNEMASA ,
YASUSHI KITAOKA ,
YASUHIRO HAYASHI ,
HIROYUKI TAKEDA ,
HIROMI FUJINO ,
RITSUKO OHTANI-KANEKO ,
KAZUAKI HIRATA  and
SATOKI UENO
YASUNARI MUNEMASA
Affiliation:
Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan
YASUSHI KITAOKA*
Affiliation:
Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan
YASUHIRO HAYASHI
Affiliation:
Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan
HIROYUKI TAKEDA
Affiliation:
Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan
HIROMI FUJINO
Affiliation:
Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan
RITSUKO OHTANI-KANEKO
Affiliation:
Department of Life Sciences, Toyo University, Itakura, Ouragun, Gunma, Japan
KAZUAKI HIRATA
Affiliation:
Department of Anatomy and Cell Biology, St. Marianna University School of Medicine, Kanagawa, Japan
SATOKI UENO
Affiliation:
Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan
*
Address correspondence and reprint requests to: Yasushi Kitaoka, Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan. E-mail: kitaoka@marianna-u.ac.jp
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Abstract

Endothelin-1 (ET-1), a potent vasoconstrictor peptide, has been implicated in the development of normal- and high-tension glaucoma. We investigated the effects of unoprostone on extracellular signal-regulated kinase (ERK) in ET-1-induced retinal ganglion cell (RGC) death and optic nerve injury. Our morphometric study showed that intravitreal injection of ET-1 led to cell loss in the RGC layer (RGCL) in 28 days. Western blot analysis showed decreased neurofilament (NF) protein in the optic nerve 28 days after ET-1 injection. In this in vivo model, increased phosphorylated ERK (p-ERK) was observed in the retina on 1 day and subsequently in the optic nerve from 7 days after ET-1 injection. Simultaneous injection of M1, as a metabolite of unoprostone, showed further increased p-ERK levels compared with ET-1 injection alone. Our morphometric study of flat-mount preparations stained with cresyl violet or retrograde labeling with a neuro-tracer and Western blot analysis of NF showed that inhibition of ERK phosphorylation led to acceleration of ET-1-induced RGC death and optic nerve damage. In addition, M1 significantly attenuated both RGC loss and the decrease in NF protein induced by ET-1. The protective effects of M1 were significantly inhibited by U0126, an ERK inhibitor. These results suggest that unoprostone has neuroprotective effects against ET-1-induced neuronal injury through ERK phosphorylation.

Keywords

Endothelin-1; ERK; UnoprostoneOptic nerveRetinal ganglion cell
Type
Research Article
Information
Visual Neuroscience , Volume 25 , Issue 2 , March 2008 , pp. 197 - 208
Copyright
Copyright © Cambridge University Press 2008

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References

REFERENCES

Alm, A. (1998). Prostaglandin derivates as ocular hypotensive agents. Progress in Retinal and Eye Research 17, 291–312.CrossRefGoogle ScholarPubMed
Ansari, H.R., Husain, S. & Abdel-Latif, A.A. (2001). Activation of p42/p44 mitogen-activated protein kinase and contraction by prostaglandin F2α, ionomycin, and thapsigargin in cat iris sphincter smooth muscle: Inhibition by PD98059, KN-93, and isoproterenol. Journal of Pharmacology and Experimental Therapeutics 299, 178–186.Google ScholarPubMed
Ansari, H.R., Kaddour-Djebbar, I. & Adbel-Latif, A.A. (2004). Effects of prostaglandin F2α, latanoprost and carbachol on phosphoinositide turnover, MAK kinases, myosin light chain phosphorylation and contraction and functional existence and expression of FP receptors in bovine iris sphincter. Experimental Eye Research 78, 285–296.CrossRefGoogle Scholar
Cellini, M., Possati, G.L., Profazio, V., Sbrocca, M., Caramazza, N. & Caramazza, R. (1997). Color Doppler imaging and plasma levels of endothelin-1 in low-tension glaucoma. Acta Ophthalmologica Scandinavica 224, 11–13.CrossRefGoogle Scholar
Crowston, J.G., Lindsey, J.D., Aihara, M. & Weinreb, R.N. (2004). Effect of latanoprost on intraocular pressure in mice lacking the prostaglandin FP receptor. Investigative Ophthalmology & Visual Science 45, 3555–3559.CrossRefGoogle ScholarPubMed
Damon, D.H. (1999). Endothelin and post-ganglionic sympathetic neurons. Clinical and Experimental Pharmacology & Physiology 26, 1000–1003.CrossRefGoogle ScholarPubMed
Desire, L., Courtois, Y. & Jeanny, J.C. (2000). Endogenous and exogenous fibroblast growth factor 2 support survival of chick retinal neurons by control of neuronal bcl-x(L) and bcl-2 expression through a fibroblast growth factor receptor 1- and ERK-dependent pathway. Journal of Neurochemistry 75, 151–163.CrossRefGoogle Scholar
Emre, M., Orgul, S., Haufschild, T., Shaw, S.G. & Flammer, J. (2005). Increased plasma endothelin-1 levels in patients with progressive open angle glaucoma. British Journal of Ophthalmology 89, 60–63.CrossRefGoogle ScholarPubMed
Freshney, N.W., Rawlinson, L., Guesdon, F., Jone, E., Cowley, S., Hsuan, J. & Saklatvala, J. (1994). Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27. Cell 78, 1039–1049.CrossRefGoogle ScholarPubMed
Hayami, K. & Unoki, K. (2001). Photoreceptor protection against constant light-induced damage by isopropyl unoprostone, a prostaglandin F (2alpha) metabolite-related compound. Ophthalmic Research 33, 203–209.CrossRefGoogle ScholarPubMed
He, S., Dibas, A., Yorio, T. & Prasanna, G. (2007). Parallel signaling pathways in endothelin-1-induced proliferation of U373MG astrocytoma cells. Experimental Biology and Medicine 232, 370–384.Google ScholarPubMed
Husain, S., Jafri, F. & Crosson, C.E. (2005). Acute effects of PGF2alpha on MMP-2 secretion from human ciliary muscle: A PKC-and ERK-dependent process. Investigative Ophthalmology & Visual Science 46, 1706–1713.CrossRefGoogle ScholarPubMed
Irving, E.A. & Bamford, M. (2002). Role of mitogen- and stress-activated kinases in ischemic injury. Journal of Cerebral Blood Flow and Metabolism 22, 631–647.CrossRefGoogle ScholarPubMed
Jakobs, T.C., Libby, R.T., Ben, Y., John, S.W.M. & Masland, R.H. (2007). Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice. Journal of Cell Biology 171, 313–325.CrossRefGoogle Scholar
Kaiser, H.J., Flammer, J., Wenk, M. & Luscher, T. (1995). Endothelin-1 plasma levels in normal-tension glaucoma: Abnormal response to postural changes. Graefe's Archive for Clinical and Experimental Ophthalmology 233, 484–488.CrossRefGoogle ScholarPubMed
Kikuchi, M., Tenneti, L. & Lipton, S.A. (2000). Role of p38 mitogen-activated protein kinase in axotomy-induced apoptosis of rat retinal ganglion cells. Journal of Neuroscience 20, 5037–5044.CrossRefGoogle ScholarPubMed
Kinkl, N., Sahel, J. & Hicks, D. (2001). Alternate FGF2-ERK1/2 signaling pathways in retinal photoreceptor and glial cells in vitro. Journal of Biological Chemistry 276, 43871–43878.CrossRefGoogle ScholarPubMed
Kitaoka, Y., Kitaoka, Y., Kwong, J.M., Ross-Cisneros, F.N., Wang, J., Tsai, R.K., Sadun, A.A. & Lam, T.T. (2006). TNF-alpha-induced optic nerve degeneration and nuclear factor-kappaB p65. Investigative Ophthalmology & Visual Science 47, 1448–1457.CrossRefGoogle ScholarPubMed
Lam, T.T., Abler, AS, Kwong, J.M. & Tso, M.O. (1999). N-methyl-D-aspartate (NMDA)-induced apoptosis in rat retina. Investigative Ophthalmology & Visual Science 40, 2319–2397.Google ScholarPubMed
Lau, J., Dang, M., Hockmann, K. & Ball, A.K. (2006). Effects of acute delivery of endothelin-1 on retinal ganglion cell loss in the rat. Experimental Eye Research 82, 132–145.CrossRefGoogle ScholarPubMed
Liu, C., Peng, M., Laties, AM. & Wen, R. (1998). Preconditioning with bright light evokes a protective response against light damage in the rat retina. Journal of Neuroscience 18, 1337–1344.CrossRefGoogle ScholarPubMed
MacCumber, M.W. & D'Anna, S.A. (1994). Endothelin receptor-binding subtypes in the human retina and choroid. Archives of Ophthalmology 112, 1231–1235.CrossRefGoogle ScholarPubMed
Marques, S.A., Taffarel, M. & Martinez, A.M.B. (2003). Participation of neurofilament proteins in axonal dark degeneration of rat's optic nerves. Brain Research 969, 1–13.CrossRefGoogle ScholarPubMed
Mukuno, H., Nakamura, M., Kanamori, A., Nagai, A., Negi, A. & Seigel, G. (2004). Unoprostone isopropyl rescues retinal progenitor cells from apoptosis in vitro. Current Eye Research 29, 457–464.CrossRefGoogle ScholarPubMed
Munemasa, Y., Ohtani-Kaneko, R., Kitaoka, Y., Kumai, T., Kitaoka, Y., Hayashi, Y., Watanabe, M., Takeda, H., Hirata, K. & Ueno, S. (2006). Pro-apoptotic role of c-Jun in NMDA-induced neurotoxicity in the rat retina. Journal of Neuroscience Research 83, 907–918.CrossRefGoogle ScholarPubMed
Munemasa, Y., Ohtani-Kaneko, R., Kitaoka, Y., Kuribayashi, K., Isenoumi, K., Kogo, J., Yamashita, K., Kumai, T., Kobayashi, S., Hirata, K. & Ueno, S. (2005). Contribution of mitogen-activated protein kinases to NMDA-induced neurotoxicity in the rat retina. Brain Research 1044, 227–240.CrossRefGoogle ScholarPubMed
Nakazawa, T., Tamai, M. & Mori, N. (2002). Brain-derived neurotrophic factor prevents axotomized retinal ganglion cell death through MAPK and PI3K signaling pathways. Investigative Ophthalmology & Visual Science 43, 3319–3326.Google ScholarPubMed
Naskar, R., Wissing, M. & Thanos, S. (2002). Detection of early neuron degeneration and accompanying microglial responses in the retina of a rat model of glaucoma. Investigative Ophthalmology & Visual Science 43, 2962–2968.Google ScholarPubMed
Oku, H., Sugiyama, T., Kojima, S., Watanabe, T. & Azuma, I. (1999). Experimental optic cup enlargement caused by endothelin-1-induced chronic optic nerve head ischemia. Survey of Ophthalmology 44, S74–S84.CrossRefGoogle ScholarPubMed
Prasanna, G., Krishnamoorthy, R., Clark, A.F., Wordinger, R.J. & Yorio, T. (2002). Human optic nerve head astrocytes as a target for endothelin-1. Investigative Ophthalmology & Visual Science 43, 2704–2713.Google ScholarPubMed
Raingeaud, J., Gupta, S., Rogers, J.S., Dickens, M., Han, J., Ulevitch, R.J. & Davis, R.J. (1995). Pro-inflammatory cytokines and environmental stress cause p38 mitgen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. Journal of Biological Chemistry 270, 7420–7426.CrossRefGoogle Scholar
Rogers, S.D., Demaster, E., Catton, M., Ghilardi, J.R., Levin, L.A., Maggio, J.E. & Mantyh, P.W. (1997). Expression of endothelin-B receptors by glia in vivo is increased after CNS injury in rats, rabbits, and humans. Experimental Neurology 145, 180–195.CrossRefGoogle ScholarPubMed
Roth, S., Shaikh, A.R., Hennelly, M.M., Li, Q., Bindokas, V. & Grahama, C.E. (2003). Mitogen-activated protein kinases and retinal ischemia. Investigative Ophthalmology & Visual Science 44, 5383–5395.CrossRefGoogle ScholarPubMed
Schinelli, S., Zanassi, P., Paolillo, M., Wang, H., Feliciello, A. & Gallo, V. (2001). Stimulation of endothelin B receptors in astrocytes induces cAMP response element-binding protein phosphorylation and c-fos expression via multiple mitogen-activated protein kinase signaling pathways. Journal of Neuroscience 21, 8842–8853.CrossRefGoogle ScholarPubMed
Sharif, N.A., Crider, J.Y., Husain, S., Kaddour-Djebbar, I., Ansari, H.R. & Abdel-Latif, A.A. (2003). Human ciliary muscle cell responses to FP-class prostaglandin analogs: Phosphoinositide hydrolysis, intracellular Ca2+ mobilization and MAP kinase activation. Journal of Ocular Pharmacology and Therapeutics 19, 437–455.CrossRefGoogle ScholarPubMed
Stitt, A.W., Chakravarthy, U., Gardiner, T.A. & Archer, D.B. (1996). Endothelin-like immunoreactovity and receptor binding in the choroids and retina. Current Eye Research 15, 111–117.CrossRefGoogle ScholarPubMed
Sugiyama, T., Moriya, S., Oku, H. & Azuma, I. (1995). Association of endothelin-1 with normal tension glaucoma: Clinical and fundamental studies. Survey of Ophthalmology 39, S49–S56.CrossRefGoogle ScholarPubMed
Susanna, R. Jr., Chew, P. & Kitazawa, Y. (2002). Current status of prostaglandin therapy: Latanoprost and unoprostone. Survey of Ophthalmology 4, S97–S104.CrossRefGoogle Scholar
Takei, K., Sato, T., Nonoyama, T., Miyauchi, T., Goto, K. & Hommura, S. (1993). A new model of transient complete obstruction of retinal vessels induced by endothelin-1 injection into the posterior vitreous body in rabbits. Graefe's Archive for Clinical and Experimental Ophthalmology 231, 476–481.CrossRefGoogle ScholarPubMed
Tezel, G., Kass, M.A., Kolker, A.E., Becker, B. & Wax, M.B. (1997). Plasma and aqueous humor endothelin levels in primary open-angle glaucoma. Journal of Glaucoma 6, 83–89.CrossRefGoogle ScholarPubMed
Tsumamoto, Y., Yamashita, K., Takumida, M., Okada, K., Mukai, S., Shinya, M., Yamashita, H. & Mishima, H.K. (2002). In situ localization of nitric oxide synthase and direct evidence of NO production in rat retinal ganglion cells. Brain Research 933, 118–129.CrossRefGoogle ScholarPubMed
Walton, M., Woodgate, A.M., Muravlev, A., Xu, R., During, M.J. & Dragunow, M. (1999). CREB phosphorylation promotes nerve cell survival. Journal of Neurochemistry 73, 1836–1842.Google ScholarPubMed
Wang, X., Zhu, C., Qiu, L., Hagberg, H., Sandberg, M. & Blomgren, K. (2003). Activation of ERK1/2 after neonatal rat cerebral hypoxia-ischemia. Journal of Neurochemistry 86, 351–362.CrossRefGoogle Scholar
Xia, Z., Dichens, M., Raingeaud, J., Davis, R.J. & Greenberg, M.E. (1995). Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270, 1326–1331.CrossRefGoogle ScholarPubMed