Induction of sulfated glycoprotein-2 (clusterin) and glial fibrillary acidic protein (GFAP) RNA expression following transient global ischemia is differentially attenuated by LY231617.
Sulfated glycoprotein-2 (SGP-2) is a secreted glycoprotein that along with GFAP has emerged as a prominent molecular marker of neurodegeneration. In the present study, we have evaluated further the relationship between SGP-2, GFAP and neurodegeneration, by examining the effects of LY231617, a potent antioxidant, on expression of SGP-2 and GFAP following four vessel occlusion (4VO). GFAP and SGP-2 RNA levels increased several fold in hippocampus and caudate nucleus in response to 30 min of 4VO. LY231617 treatment markedly attenuated the induction of GFAP RNA in both hippocampus and caudate nucleus, consistent with the significant neuroprotection observed histologically. In contrast, LY231617 treatment blunted SGP-2 RNA expression only in the hippocampus; SGP-2 RNA expression in caudate nucleus was similar to vehicle-treated 4VO, despite the marked attenuation of neuronal damage in both areas by LY231617. These data suggest region-specific differential regulation of SGP-2 and GFAP RNA induction.
Lilly Research Laboratories, CNS Research, Eli Lilly and Company, Indianapolis, IN 46285, USA.
P C
PC
May
J A
JA
Clemens
J A
JA
Panetta
E B
EB
Smalstig
D
D
Stephenson
K S
KS
Fuson
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D015415:Biomarkers / Q000737:chemistry; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002421:Caudate Nucleus / Q000098:blood supply / Q000378:metabolism; D051152:Clusterin; D003250:Constriction; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D018832:Molecular Chaperones; D009410:Nerve Degeneration / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D015415:Biomarkers; D051152:Clusterin; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D002084:Butylated Hydroxytoluene; C081064:LY 231617