Stress response to hypoxia in gerbil brain: HO-1 and Mn SOD expression and glial activation.
Hypoxic preconditioning has been shown to induce neuroprotection against a subsequent damaging insult. In order to study the underlying molecular and cellular mechanisms of hypoxic preconditioning, we investigated, in gerbil hippocampus, the effects in vivo of transient exposure to hypoxia (4% O(2) for 6 min followed by either 48 h or 7 days of reoxygenation) (i) on the induction of 72 kDa heat shock protein (HSP72), heme oxygenase-1 (HO-1) and manganese superoxide dismutase (Mn SOD) as assessed by Western immunoblotting and (ii) on the astroglial and microglial activation as detected by both immunohistochemistry and Western immunoblotting for GFAP, and histochemistry for isolectin B4, respectively. Our data show that, although hypoxia and subsequent reoxygenation led to neither neuronal damage nor HSP72 induction in gerbil hippocampus, it induced a progressive and sustained expression of HO-1 and Mn SOD. As expected from the absence of neuronal death, hypoxia was not associated with microglial activation but led to a significant astrocytic activation. These findings demonstrate that transient hypoxia enhances the antioxidative enzymatic defenses of the brain, which are susceptible to increased tolerance against a subsequent damaging insult.
Unité de Biochimie-Pharmacologie-Toxicologie, Laboratoire de Pharmacodynamie, Faculté de Pharmacie, BP 87900, 21079 Dijon Cedex, France.
P
P
Garnier
C
C
Demougeot
N
N
Bertrand
A
A
Prigent-Tessier
C
C
Marie
A
A
Beley
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D015153:Blotting, Western; D005849:Gerbillinae; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism*; D007150:Immunohistochemistry; D037102:Lectins / Q000378:metabolism; D008297:Male; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D013312:Stress, Physiological; D013482:Superoxide Dismutase / Q000096:biosynthesis*
D005904:Glial Fibrillary Acidic Protein; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D037102:Lectins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase