Proteomic identification of a novel protein regulated in CA1 and CA3 hippocampal regions during intermittent hypoxia.
The CA1 and CA3 regions of the hippocampus markedly differ in their susceptibility to hypoxia in general, and more particularly to the intermittent hypoxia (IH) that characterizes sleep apnea. We used proteomic analysis to build a database of proteins expressed in normoxic CA1 and CA3. The current hippocampus protein database identifies 106 proteins. A hypothetical protein with accession number AK006737 (gimid R:12839969) was strongly upregulated in the CA1, but not CA3 hippocampal region. Bioinformatic analysis revealed that the unknown protein contained a high stringency protein kinase e binding site. Domain analysis demonstrated the presence of a conserved sequence indicative of macrophage scavenger receptors. Using proteomic analysis we have previously demonstrated that acute (6 h) IH-mediated CA1 injury results from complex interactions between pathways involving increased metabolism, induction of stress-induced proteins and apoptosis, and ultimately disruption of structural proteins and cell integrity. The current findings identify a hypothetical protein that may play a key role in the response of CA1 to IH. These findings provide initial insights into mechanisms underlying differences in susceptibility to hypoxia in neural tissue and demonstrate how proteomic analysis can be used to generate new hypotheses, which define neuronal adaptation to IH.
Klein
Jon B
JB
Department of Medicine, Core Proteomics Laboratory, Kidney Disease Program, University of Louisville, 570 South Preston Street, Suite 102, Louisville, KY 40202, USA. jon.klein@louisville.edu
Gozal
David
D
Pierce
William M
WM
Thongboonkerd
Visith
V
Scherzer
Janice A
JA
Sachleben
Leroy R
LR
Guo
Shang Z
SZ
Cai
Jian
J
Gozal
Evelyne
E
D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D001923:Brain Chemistry; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D015180:Electrophoresis, Gel, Two-Dimensional; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D009419:Nerve Tissue Proteins / Q000302:isolation & purification* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000378:metabolism; D051116:Receptors, Scavenger; D020539:Sequence Analysis, Protein / Q000379:methods; D013997:Time Factors
D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D011493:Protein Kinase C