Heme oxygenase-1 gene therapy for prevention of vasospasm in rats

Ono, Shigeki; Komuro, Taro; Macdonald, R. Loch

doi:10.3171/jns.2002.96.6.1094

Cited by 65 publications

(63 citation statements)

References 51 publications

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“…It is interesting to note that one of the major pathological complications following such a haemorrhage is ischaemia brought on by delayed vasospasm (23). The vasoactive F 2 -isoprostanes have also been identified in the cerebrospinal fluid following haemorrhaging (24,25). The presence of Mb-X in the urine of patients diagnosed with rhabdomyolysis and the presence of Hb-X in the cerebrospinal fluid of patients with suggests that these haem proteins are a major driving force of lipid oxidation reactions and hence may be important in understanding the mechanisms of pathological complications.…”

Section: Introductionmentioning

confidence: 99%

Histidine and not tyrosine is required for the Peroxide‐induced formation of haem to protein cross‐linked myoglobin

et al. 2007

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SummaryPeroxide-induced oxidative modifications of haem proteins such as myoglobin and haemoglobin can lead to the formation of a covalent bond between the haem and globin. These haem to protein cross-linked forms of myoglobin and haemoglobin are cytotoxic and have been identified in pathological conditions in vivo. An understanding of the mechanism of haem to protein cross-link formation could provide important information on the mechanisms of the oxidative processes that lead to pathological complications associated with the formation of these altered myoglobins and haemoglobins. We have re-examined the mechanism of the formation of haem to protein cross-link to test the previously reported hypothesis that the haem forms a covalent bond to the protein via the tyrosine 103 residue (Catalano, C. E., Choe, Y. S., Ortiz de Montellano, P. R., J. Biol. Chem. 1989, 10534 -10541).Comparison of native horse myoglobin, recombinant sperm whale myoglobin and Tyr 103 ! Phe sperm whale mutant shows that, contrary to the previously proposed mechanism of haem to protein cross-link formation, the absence of tyrosine 103 has no impact on the formation of haem to protein cross-links. In contrast, we have found that engineered myoglobins that lack the distal histidine residue either cannot generate haem to protein cross-links or show greatly suppressed levels of modified protein. Moreover, addition of a distal histidine to myoglobin from Aplysia limacina, that naturally lacks this histidine, restores the haem protein's capacity to generate haem to protein cross-links. The distal histidine is, therefore, vital for the formation of haem to protein cross-link and we explore this outcome. IUBMB Life, 59: 477-489, 2007

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Section: Introductionmentioning

confidence: 99%

Histidine and not tyrosine is required for the Peroxide‐induced formation of haem to protein cross‐linked myoglobin

et al. 2007

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“…( 11 ) reported a case of human HO-1 deficiency associated with endothelial cell injury, vulnerability to stress, anemia, and growth retardation. Conversely, experimental HO-1 gene delivery has been shown to result in amelioration of atherosclerosis ( 12 ), injury-induced vascular neointima formation ( 13 ), ischemic heart disease ( 14 ), renal ischemia/ reperfusion injury ( 15 ), hypoxia-induced lung injury ( 16 ) and liver ischemia/reperfusion injury ( 17 ), as well as improvement of vascular function ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Reduced Expression of Heme Oxygenase-1 in Patients with Coronary Atherosclerosis

et al. 2007

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“…Although the present results suggest that gene transfer driven by the enhanced GFAP promoter may be a useful tool for in vitro experiments, its efficacy in vivo remains to be defined. Precedent for therapeutic gene transfer using a viral vector in CNS hemorrhage models has been provided by Ono et al, who observed that adenoviral transfer of the HO-1 gene attenuated basilar artery vasospasm in a rat model of subarachnoid hemorrhage (Ono et al, 2002). In addition, Masada et al reported that intraventricular injection of an adenovirus encoding interleukin-1 receptor antagonist attenuated tissue edema and the local inflammatory response after experimental striatal hemorrhage (Masada et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Astrocyte-specific heme oxygenase-1 hyperexpression attenuates heme-mediated oxidative injury

Benvenisti-Zarom

Regan

2007

Neurobiology of Disease

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In prior studies, we have observed that HO activity protects astrocytes from heme-mediated injury, but paradoxically increases neuronal injury. In this study, we tested the hypothesis that an adenovirus encoding the human HO-1 gene driven by an enhanced glial fibrillary acidic protein promoter (Ad-GFAP-HO-1) would increase HO-1 expression selectively in astrocytes, and provide cytoprotection. Treatment with 100 MOI Ad-GFAP-HO-1 for 24h resulted in HO-1 expression that was 6.4-fold higher in cultured primary astrocytes than in neurons. Astrocyte HO activity was increased by approximately fourfold over baseline, which was sufficient to reduce cell death after 24 h hemin exposure by 60%, as assessed by both MTT and LDH release assays. A similar reduction in cell protein oxidation, quantified by carbonyl assay, was also observed. These results suggest that HO-1 transgene expression regulated by an enhanced GFAP promoter selectively increases HO-1 expression in astrocytes, and is cytoprotective. Further investigation of this strategy in vivo is warranted.

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Heme oxygenase-1 gene therapy for prevention of vasospasm in rats

Abstract: These results show that overexpression of HO-1 inhibits arterial contractions induced by hemoglobin and can reduce vasospasm after experimental SAH.

Cited by 65 publications

References 51 publications

Histidine and not tyrosine is required for the Peroxide‐induced formation of haem to protein cross‐linked myoglobin

Histidine and not tyrosine is required for the Peroxide‐induced formation of haem to protein cross‐linked myoglobin

Reduced Expression of Heme Oxygenase-1 in Patients with Coronary Atherosclerosis

Astrocyte-specific heme oxygenase-1 hyperexpression attenuates heme-mediated oxidative injury

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