CORTICOSTERONE REGULATES HEME OXYGENASE-2 AND NO SYNTHASE TRANSCRIPTION AND PROTEIN EXPRESSION IN RAT-BRAIN

WEBER C., EKE B., MAINES M.

JOURNAL OF NEUROCHEMISTRY, cilt.63, sa.3, ss.953-962, 1994 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 63 Sayı: 3
  • Basım Tarihi: 1994
  • Doi Numarası: 10.1046/j.1471-4159.1994.63030953.x
  • Dergi Adı: JOURNAL OF NEUROCHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.953-962
  • Anahtar Kelimeler: HEME OXYGENASE-2, NITRIC OXIDE SYNTHASE, CORTICOSTERONE, CARBON MONOXIDE, PROTEIN EXPRESSION, RAT BRAIN, NITRIC-OXIDE SYNTHASE, NEURONAL NADPH DIAPHORASE, MESSENGER-RNA, CARBON-MONOXIDE, BILIVERDIN REDUCTASE, HIPPOCAMPAL DAMAGE, RAPID INDUCTION, CELL-DEATH, GLUCOCORTICOIDS, LOCALIZATION
  • Ankara Üniversitesi Adresli: Hayır

Özet

Heme oxygenase (HO)-1 and -2 produce carbon monoxide, which is suspected, as is nitric oxide (NO), to function as a neuronal messenger. We report on glucocorticoid-mediated modulation of HO-2 and NO synthase expression in brain and the differential response of the two proteins to corticosterone in different brain regions. Corticosterone treatment (40 mg/kg, 20 days) had oppos ing effects on HO-2 and NO synthase transcript levels: increasing the 1.3- and 1.9-kb HO-2 mRNAs and decreasing that of the brain-specific 10.5-kb NO synthase. Corticosterone did not uniformly affect HO-2 protein expression in all regions, but appeared to cause a universal reduction in NO synthase, e.g., HO-2 was decreased in hippocampus(CA1 and dentate gyrus), but not in cerebellum. In contrast, NADPH diaphorase staining was reduced in hippocampus and in molecular and granule layers of cerebellum (not detected in Purkinje cells). Striking deficits in neuronal morphology and number of diaphorase-staining neurons were observed in the lateral tegmental area, paraventricular nucleus, and frontal cortex; HO-2 expression was only selectively affected. In cerebellum, activity of NO synthase, but not that of HO, was reduced. Consistent with the possibility that carbon monoxide can generate cyclic GMP, the change in cyclic GMP level did not mirror the decrease in NO synthase. We suggest that glucocorticoid-mediated deficits in hippocampal functions may reflect their negative effect on messenger-generating systems.