title: The protective effect of growth hormone on Cu/Zn superoxide dismutase-mutant motor neurons.
abstract: BACKGROUND
  Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of motor neurons. The gene encoding Cu/Zn superoxide dismutase (SOD1) is responsible for 20% of familial ALS cases. Growth hormone (GH) concentrations are low in the cerebrospinal fluid of patients with ALS; however, its association with motoneuronal death is not known. We tested the neuroprotective effects of GH on human SOD-1-expressing cultured motor neurons and SOD1G93A transgenic mice.
  
  
  RESULTS
  In cultured motor neurons, cytotoxicity was induced by A23187, GNSO, or homocysteine, and the effects of GH were determined by MTT, bax, PARP cleavage pattern, Hoechst nuclear staining, MAPK, and PI3K assay. In SOD-1 transgenic mice, rotarod motor performance was evaluated. Survival analysis of motoneuronal loss was done using cresyl violet, GFAP, and Bcl-2 staining. GH prevents motorneuronal death caused by GSNO and homocysteine, but not that by A23187. It activates MAPK and PI3K. GH-treated mice showed prolonged survival with improved motor performance and weight loss. GH decreased cresyl violet positive motoneuronal loss with strong Bcl-2 and less GFAP immunoreactivity.
  
  
  CONCLUSIONS
  Our results demonstrate that GH has a protective effect on mutant SOD-1-expressing motor neurons.
authors: Department of Veterinary Internal Medicine and Geriatrics, Kangwon National University, Gangwondo, South Korea. jychung77@gmail.com.
authors: Jin-Young
authors: JY
authors: Chung
authors: Department of Neurology, Seoul National University Hospital, 101 Daehakro, Chongno-ku, 110-744, Seoul, South Korea. jsskim03@gmail.com.
authors: Hyun-Jung
authors: HJ
authors: Kim
authors: Department of Neurology, Seoul National University Hospital, 101 Daehakro, Chongno-ku, 110-744, Seoul, South Korea. kimmanho@snu.ac.kr.|Protein Metabolism Medical Research Center, College of Medicine, Seoul National University, 101 Daehakro, Chongno-ku, 110-744, Seoul, South Korea. kimmanho@snu.ac.kr.
authors: Manho
authors: M
authors: Kim
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D009154:Mutation; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D018696:Neuroprotective Agents; C000606290:SOD1 protein, human; D019382:Human Growth Hormone; C000606291:Sod1 protein, mouse; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases
references: J Neurosci. 2001 Sep 1;21(17):6569-76
references: 11517246
references: Ann Neurol. 2005 Aug;58(2):258-65
references: 16049935
references: Mol Cell Neurosci. 2001 Dec;18(6):619-31
references: 11749038
references: Mol Cell Endocrinol. 2002 Feb 25;188(1-2):1-7
references: 11911939
references: Neuroreport. 2002 Mar 25;13(4):377-81
references: 11930144
references: J Cereb Blood Flow Metab. 2002 Jul;22(7):798-809
references: 12142565
references: Neuroreport. 2002 Jul 2;13(9):1131-5
references: 12151755
references: Endocrinology. 2002 Oct;143(10):4113-22
references: 12239123
references: Int J Dev Neurosci. 2002 Oct;20(6):521-6
references: 12392756
references: Brain Res. 2003 Mar 28;967(1-2):226-34
references: 12650983
references: Int J Dev Biol. 2003 Feb;47(1):41-9
references: 12653250
references: Pharmacol Ther. 2003 Jun;98(3):379-414
references: 12782245
references: Neuroreport. 2003 May 23;14(7):1051-4
references: 12802201
references: Growth Horm IGF Res. 2003 Aug;13 Suppl A:S18-21
references: 12914720
references: Annu Rev Neurosci. 2004;27:723-49
references: 15217349
references: Neurology. 1976 May;26(5):460-5
references: 944398
references: J Clin Endocrinol Metab. 1980 Nov;51(5):1089-92
references: 6999006
references: Cytometry. 1992;13(2):137-43
references: 1372208
references: Psychoneuroendocrinology. 1993;18(3):183-90
references: 8516423
references: Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3393-7
references: 8159758
references: Science. 1994 Jun 17;264(5166):1772-5
references: 8209258
references: J Neurosurg Sci. 1994 Mar;38(1):43-9
references: 7965141
references: Endocr Dev. 2005;9:160-9
references: 15879696
references: J Neurol. 2012 Jan;259(1):132-8
references: 21706151
references: J Neurol Sci. 2005 Sep 15;236(1-2):1-7
references: 16024047
references: Neurosci Lett. 2006 Mar 6;395(2):103-7
references: 16356650
references: Clin Endocrinol (Oxf). 2006 Sep;65(3):385-8
references: 16918961
references: Nat Rev Neurosci. 2006 Sep;7(9):710-23
references: 16924260
references: Eur J Neurol. 2006 Dec;13(12):1340-5
references: 17116217
references: Neurosci Lett. 2007 Feb 21;413(3):265-9
references: 17174029
references: Growth Horm IGF Res. 2007 Aug;17(4):315-22
references: 17482859
references: J Endocrinol Invest. 2007 Oct;30(9):767-70
references: 17993769
references: Acta Neurol Scand. 1999 Nov;100(5):317-21
references: 10536919
references: J Neurochem. 1999 Dec;73(6):2460-8
references: 10582606
references: Science. 2000 Apr 14;288(5464):283-4
references: 10777410
references: Nat Med. 2000 May;6(5):513-9
references: 10802706
references: Horm Res. 2000;53 Suppl 3:37-41
references: 10971102
references: Amino Acids. 2000;19(1):363-71
references: 11026507
references: Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13901-6
references: 11095709
references: Mol Endocrinol. 2001 Feb;15(2):308-18
references: 11158336
references: Neuroscience. 2001;104(3):677-87
references: 11440801
references: Semin Neurol. 2001 Jun;21(2):131-9
references: 11442322
references: Ann N Y Acad Sci. 1994 Dec 15;747:162-71
references: 7847669
references: Neurosci Lett. 1995 Oct 20;199(2):152-4
references: 8584246
references: J Neurobiol. 1997 Feb;32(2):202-12
references: 9032662
references: Am J Physiol. 1998 Jun;274(6 Pt 2):R1704-11
references: 9608025
references: J Cell Biol. 2005 Jan 17;168(2):193-9
references: 15657392
references: Exp Mol Med. 2007 Oct 31;39(5):574-82
references: 18059133
references: J Steroid Biochem Mol Biol. 2008 Feb;108(3-5):318-26
references: 18252241
references: Neuropharmacology. 2008 Jun;54(7):1112-9
references: 18436268
references: Neurology. 2008 Nov 25;71(22):1770-5
references: 19029516
references: Eur J Neurol. 2010 May;17(5):666-71
references: 20002733
references: Nat Rev Neurosci. 2001 Nov;2(11):806-19
references: 11715057