Galantamine and carbon monoxide protect brain microvascular endothelial cells by heme oxygenase-1 induction

Atsunori Nakao, David J. Kaczorowski, Brian S. Zuckerbraun, Jing Lei, Gaetano Faleo, Kentaro Deguchi, Kenneth R. McCurry, Timothy R. Billiar, Shinichi Kanno

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Galantamine, a reversible inhibitor of acetylcholine esterase (AChE), is a novel drug treatment for mild to moderate Alzheimer's disease and vascular dementia. Interestingly, it has been suggested that galantamine treatment is associated with more clinical benefit in patients with mild-to-moderate Alzheimer disease compared to other AChE inhibitors. We hypothesized that the protective effects of galantamine would involve induction of the protective gene, heme oxygenase-1 (HO-1), in addition to enhancement of the cholinergic system. Brain microvascular endothelial cells (mvECs) were isolated from spontaneous hypertensive rats. Galantamine significantly reduced H2O2-induced cell death of mvECs in association with HO-1 induction. These protective effects were completely reversed by nuclear factor-κB (NF-κB) inhibition or HO inhibition. Furthermore, galantamine failed to induce HO-1 in mvECs which lack inducible nitric oxide synthase (iNOS), supplementation of a nitric oxide (NO) donor or iNOS gene transfection on iNOS-deficient mvECs resulted in HO-1 induction with galantamine. These data suggest that the protective effects of galantamine require NF-κB activation and iNOS expression, in addition to HO-1. Likewise, carbon monoxide (CO), one of the byproducts of HO, up-regulated HO-1 and protected mvECs from oxidative stress in a similar manner. Our data demonstrate that galantamine mediates cytoprotective effects on mvECs through induction HO-1. This pharmacological action of galantamine may, at least in part, account for the superior clinical efficacy of galantamine in vascular dementia and Alzheimer disease.

Original languageEnglish
Pages (from-to)674-679
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume367
Issue number3
DOIs
Publication statusPublished - Mar 14 2008
Externally publishedYes

Fingerprint

Galantamine
Heme Oxygenase-1
Endothelial cells
Carbon Monoxide
Brain
Endothelial Cells
Nitric Oxide Synthase Type II
Alzheimer Disease
Vascular Dementia
Esterases
Acetylcholine
Genes
Drug therapy
Oxidative stress
Nitric Oxide Donors
Cell death
Vascular Diseases
Cholinergic Agents
Transfection
Byproducts

Keywords

  • Alzheimer disease
  • Carbon monoxide
  • Galantamine
  • Heme oxygenase
  • Inducible nitric oxide synthase
  • Nuclear factor-κB
  • Vascular dementia
  • Vascular endothelial cells

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Galantamine and carbon monoxide protect brain microvascular endothelial cells by heme oxygenase-1 induction. / Nakao, Atsunori; Kaczorowski, David J.; Zuckerbraun, Brian S.; Lei, Jing; Faleo, Gaetano; Deguchi, Kentaro; McCurry, Kenneth R.; Billiar, Timothy R.; Kanno, Shinichi.

In: Biochemical and Biophysical Research Communications, Vol. 367, No. 3, 14.03.2008, p. 674-679.

Research output: Contribution to journalArticle

Nakao, A, Kaczorowski, DJ, Zuckerbraun, BS, Lei, J, Faleo, G, Deguchi, K, McCurry, KR, Billiar, TR & Kanno, S 2008, 'Galantamine and carbon monoxide protect brain microvascular endothelial cells by heme oxygenase-1 induction', Biochemical and Biophysical Research Communications, vol. 367, no. 3, pp. 674-679. https://doi.org/10.1016/j.bbrc.2007.12.152
Nakao, Atsunori ; Kaczorowski, David J. ; Zuckerbraun, Brian S. ; Lei, Jing ; Faleo, Gaetano ; Deguchi, Kentaro ; McCurry, Kenneth R. ; Billiar, Timothy R. ; Kanno, Shinichi. / Galantamine and carbon monoxide protect brain microvascular endothelial cells by heme oxygenase-1 induction. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 367, No. 3. pp. 674-679.
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AU - Faleo, Gaetano

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