The mechanism of heme oxygenase-1 action involved in the enhancement of neurotrophic factor expression

Neuropharmacology
Shih-Ya HungWen-Mei Fu

Abstract

Heme oxygenase-1 (HO-1) is up-regulated in response to oxidative stress and catalyzes the degradation of pro-oxidant heme to carbon monoxide (CO), iron and bilirubin. Bilirubin is a potent antioxidant and neuroprotectant. Neurotrophic factors of BDNF and GDNF also play important roles in survival and morphological differentiation of dopaminergic neurons. We have previously found that HO-1 induction by adenovirus containing human HO-1 gene (Ad-HO-1) in substantia nigra of rat increases BDNF and GDNF expression. We here further examined the possible mechanism of HO-1 action involved in the enhancement of neurotrophic factor expression. Treatment of anti-BDNF/GDNF antibody significantly enhanced dopaminergic neuronal death, whereas Ad-HO-1 co-treatment was able to antagonize the apoptosis-inducing effect of these antibodies. The confocal imaging shows that HO-1 induction appeared in dopaminergic neuron, astrocyte and microglia at 24 h after injecting Ad-HO-1. HO-1 induced-BDNF/GDNF mRNA expression in substantia nigra was 26/21 folds of that of the contralateral Ad-injected side. The downstream product bilirubin increased GDNF expression through ERK and PI3K-Akt pathways, and also enhanced NFkappaB (p65 and p50) nuclear translocati...Continue Reading

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Citations

Oct 15, 2011·Nihon eiseigaku zasshi. Japanese journal of hygiene·Tin Tin Win-ShweHidekazu Fujimaki
Mar 9, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hiroyuki SakataPak H Chan
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May 1, 2017·Molecular Neurobiology·Priscila Machado RosaAndré Quincozes-Santos
Dec 10, 2019·Oxidative Medicine and Cellular Longevity·Solomon Habtemariam
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Jul 2, 2021·Oxidative Medicine and Cellular Longevity·Chih-Chung LinChuen-Mao Yang

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