title: Downregulation of PEBP1 in rat brain cortex in hypoxia.
abstract: In order to understand dementia and other ailments associated with high altitude hypoxia, adult Sprague Dawley male rats were exposed to simulated conditions of high altitude (7,500 m above sea level, 59 mmHg) for a period of 5 days and analyzed for changes in neuronal proteome by 2-D sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein extracts obtained from the brain cortex and hippocampus of the hypoxic rats were separated by 2-D gel electrophoresis. Differentially expressed proteins (analysis by 2-D gel analysis software, Bio-2D, Vilber-Lourmat, France and Delta2d, Decodon, Germany) were subjected to matrix-assisted laser desorption/ionization time-of-flight analysis. Among the proteins identified, the spot corresponding to pI 5.4 and molecular weight 21 kDa, identified as phosphatidylethanolamine binding protein (PEBP1), was consistently lowered (54%) in hypoxic cortex samples. PEBP1, also known as Raf kinase inhibitor protein, is a precursor of hippocampus cholinergic neurostimulatory peptide (HCNP). Western blot analysis revealed elevated phospho-extracellular signal-regulated kinase in hypoxic rat cortex samples, indicating activation of Raf/mitogen-activated protein kinase pathway under hypoxia. Lowered HCNP levels leading to 23% decrease in choline acetyltransferase and 63% increase in acetylcholinesterase activity were detected in hypoxic rat brain cortex, while no significant change was noted in hippocampus. Since PEBP1 is lowered in a number of neurological disorders associated with dementia, we speculate that lowered expression of PEBP1 might be responsible for dementia associated with high-altitude hypoxia. Further studies targeting PEBP1 might give clues about signaling pathways associated with hypoxia and dementia.
authors.affiliation: Department of Biochemistry, Osmania University, Hyderabad, 500007, Andhra Pradesh, India.
authors.forename: Sandeepta
authors.initials: S
authors.lastname: Burgula
authors.forename: Rajesh
authors.initials: R
authors.lastname: Medisetty
authors.forename: Nalini
authors.initials: N
authors.lastname: Jammulamadaka
authors.forename: Sairam
authors.initials: S
authors.lastname: Musturi
authors.forename: Govindan
authors.initials: G
authors.lastname: Ilavazhagan
authors.forename: Surya S
authors.initials: SS
authors.lastname: Singh
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000378:metabolism; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009479:Neuropeptides; C550693:PEBP1 protein, rat; D049488:Phosphatidylethanolamine Binding Protein; C075274:hippocampal cholinergic neurostimulating peptide; D002795:Choline O-Acetyltransferase; D048049:Extracellular Signal-Regulated MAP Kinases; D000110:Acetylcholinesterase
references.citation: J Biol Chem. 2004 Oct 29;279(44):45855-64
references.pmid: 15302887
references.citation: High Alt Med Biol. 2008 Spring;9(1):63-75
references.pmid: 18331222
references.citation: Am J Physiol. 1998 Sep;275(3):L461-8
references.pmid: 9728040
references.citation: Wien Med Wochenschr. 2002;152(3-4):72-6
references.pmid: 11925775
references.citation: J Neurosci Res. 1996 Aug 01;45(3):202-15
references.pmid: 8841981
references.citation: Brain Res Dev Brain Res. 2001 Jan 31;126(1):117-20
references.pmid: 11172893
references.citation: Biochem Pharmacol. 1961 Jul;7:88-95
references.pmid: 13726518
references.citation: Brain Res. 2003 Mar 7;965(1-2):194-202
references.pmid: 12591138
references.citation: J Neurochem. 1988 Jun;50(6):1914-23
references.pmid: 3373218
references.citation: J Neurochem. 1978 Oct;31(4):757-60
references.pmid: 212531
references.citation: Int J Sports Med. 1993 May;14(4):232-4
references.pmid: 8325724
references.citation: Am J Med. 2006 Feb;119(2):168.e1-6
references.pmid: 16443427
references.citation: Circ Res. 1996 Jan;78(1):82-90
references.pmid: 8603510
references.citation: Neurobiol Aging. 2006 Apr;27(4):614-23
references.pmid: 15941609
references.citation: Nat Med. 1995 Oct;1(10):1082-5
references.pmid: 7489367
references.citation: Brain Res. 1996 Jan 8;706(1):57-70
references.pmid: 8720492
references.citation: Behav Brain Res. 2007 Feb 27;177(2):308-14
references.pmid: 17218023
references.citation: J Neurochem. 2006 Nov;99(4):1133-41
references.pmid: 17018026
references.citation: Oncol Rep. 2006 Sep;16(3):451-6
references.pmid: 16865242
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2005 May 5;819(1):115-29
references.pmid: 15797529
references.citation: J Biol Chem. 1968 Jul 25;243(14):3864-70
references.pmid: 5690817
references.citation: Int J Biometeorol. 1966 Jul;10(1):63-9
references.pmid: 6003442
references.citation: J Biol Chem. 2003 Apr 11;278(15):13061-8
references.pmid: 12551925
references.citation: Alzheimer Dis Assoc Disord. 1995;9 Suppl 2:23-8
references.pmid: 8534419
references.citation: Anal Biochem. 1984 Apr;138(1):141-3
references.pmid: 6731838
references.citation: Electrophoresis. 1999 Dec;20(18):3551-67
references.pmid: 10612281
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: Methods Mol Biol. 1997;64:165-73
references.pmid: 9116819
references.citation: Proc Natl Acad Sci U S A. 1984 Apr;81(8):2567-71
references.pmid: 6585816
references.citation: J Neuropathol Exp Neurol. 2002 Feb;61(2):176-85
references.pmid: 11853019
references.citation: J Biol Chem. 2004 Mar 26;279(13):13054-64
references.pmid: 14724289
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18727-32
references.pmid: 17121991
references.citation: J Biol Chem. 2001 Jan 5;276(1):535-40
references.pmid: 11034991
references.citation: J Clin Invest. 1990 Sep;86(3):900-8
references.pmid: 2394839
references.citation: Mol Cell Biol. 2000 May;20(9):3079-85
references.pmid: 10757792
references.citation: Cell Signal. 2008 May;20(5):935-41
references.pmid: 18294816
references.citation: Brain Res. 1991 Jul 19;554(1-2):264-71
references.pmid: 1933308
references.citation: Biol Reprod. 2002 Jul;67(1):232-9
references.pmid: 12080022
references.citation: Cell Signal. 2008 Jan;20(1):1-9
references.pmid: 17706925
references.citation: Adv Cancer Res. 2004;91:169-200
references.pmid: 15327891
references.citation: Prog Neurobiol. 2003 Feb;69(3):193-211
references.pmid: 12758110
references.citation: Nature. 1999 Sep 9;401(6749):173-7
references.pmid: 10490027
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17213-8
references.pmid: 16275899
references.citation: J Neurochem. 2002 Oct;83(2):331-45
references.pmid: 12423243