Heme oxygenase expression in human central nervous system disorders

Schipper, Hyman M.

doi:10.1016/j.freeradbiomed.2004.09.015

Cited by 227 publications

(175 citation statements)

References 117 publications

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“…In the normal brain and in cerebral vessels, HO-1 is undetectable, with the exception of few neuronal populations, mainly olfactory and hippocampal neurons [37][38][39][40][41][42]. In sharp contrast to other tissues, brain and cerebrovascular HO-1 is not readily induced by oxidative stress, with the exception of very limited array of strong pro-oxidant signals.…”

Section: Heme Oxygenase Isoforms In Cerebral Circulationmentioning

confidence: 98%

“…In sharp contrast to other tissues, brain and cerebrovascular HO-1 is not readily induced by oxidative stress, with the exception of very limited array of strong pro-oxidant signals. Among few described pathophysiological interventions that upregulate HO-1 in the brain in vivo, are hemorrhage [41][42][43] and hyperthermia [38]. However, epileptic seizures that cause a burst of oxidative stress in the brain failed to induce HO-1 in the brain parenchyma or in cerebral vasculature within 4-24 h [39].…”

Section: Heme Oxygenase Isoforms In Cerebral Circulationmentioning

confidence: 99%

“…However, epileptic seizures that cause a burst of oxidative stress in the brain failed to induce HO-1 in the brain parenchyma or in cerebral vasculature within 4-24 h [39]. HO-1 upregulation in the brain (neurons and glia) has been described in patients with the chronic neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases (reviewed in [42]). …”

Section: Heme Oxygenase Isoforms In Cerebral Circulationmentioning

confidence: 99%

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Cerebroprotective Functions of HO-2

Parfenova¹,

Leffler²

2008

CPD

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The constitutive isoform of heme oxygenase, HO-2, is highly expressed in the brain and in cerebral vessels. HO-2 functions in the brain have been evaluated using pharmacological inhibitors of the enzyme and HO-2 gene deletion in in vivo animal models and in cultured cells (neurons, astrocytes, cerebral vascular endothelial cells). Rapid activation of HO-2 via posttranslational modifications without upregulation of HO-2 expression or HO-1 induction coincides with the increase in cerebral blood flow aimed at maintaining brain homeostasis and neuronal survival during seizures, hypoxia, and hypotension. Pharmacological inhibition or gene deletion of brain HO-2 exacerbates oxidative stress induced by seizures, glutamate, and inflammatory cytokines, and causes cerebral vascular injury. Carbon monoxide (CO) and bilirubin, the end products of HO-catalyzed heme degradation, have distinct cytoprotective functions. CO, by binding to a heme prosthetic group, regulates the key components of cell signaling, including BK Ca channels, guanylyl cyclase, NADPH oxidase, and the mitochondria respiratory chain. Cerebral vasodilator effects of CO are mediated via activation of BK Ca channels and guanylyl cyclase. CO, by inhibiting the major components of endogenous oxidantgenerating machinery, NADPH oxidase and the cytochrome C oxidase of the mitochondrial respiratory chain, blocks formation of reactive oxygen species. Bilirubin, via redox cycling with biliverdin, is a potent oxidant scavenger that removes preformed oxidants. Overall, HO-2 has dual housekeeping cerebroprotective functions by maintaining autoregulation of cerebral blood flow aimed at improving neuronal survival in a changing environment, and by providing an effective defense mechanism that blocks oxidant formation and prevents cell death caused by oxidative stress. KeywordsHeme oxygenase; cerebral protection; cerebrovascular disease; oxidative stress; seizures; carbon monoxide; bilirubin Vasodilator role of CO in cerebral circulation A. Vasoactive effects of exogenous CO in cerebral vesselsExperimental studies in newborn pigs conducted using in vivo and in vitro approaches demonstrate that exogenous CO is a potent vasodilator in cerebral circulation [1][2][3][4][5][6][7]. CO can be delivered to the brain as CO gas dissolved in a physiological buffer or as recently introduced CO-releasing molecules (CO-RMs) that release CO on illumination (dimanganese decacarbonyl, DMDC) or when dissolved in physiologically buffered solutions (sodium boranocarbonate, CO-RM-A1) [8,9]. In vivo, CO, DMDC and CORM-A1 applied directly to the brain surface under the cranial window at concentrations ≥10 −7 M causes dilation of pial arterioles, major resistance brain vessels that define the cerebral blood

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Section: Heme Oxygenase Isoforms In Cerebral Circulationmentioning

confidence: 98%

Section: Heme Oxygenase Isoforms In Cerebral Circulationmentioning

confidence: 99%

Section: Heme Oxygenase Isoforms In Cerebral Circulationmentioning

confidence: 99%

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Cerebroprotective Functions of HO-2

Parfenova¹,

Leffler²

2008

CPD

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“…The expression of each gene differs by cell type, tissue distribution and regulation [163]. The regulation of HO-1 expression in mammalian cells is very complex.…”

Section: The Oxidant Potential Of Heme Is Neutralized By Multiple Hemmentioning

confidence: 99%

Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinases

Mense

2006

Cell Res

253

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“…The involvement of CO in regulating blood pressure and its production in response to ischemic and metabolic stress suggest roles for CO in the pathogenesis of cardiovascular disease. Similarly, the emerging evidence that CO plays roles in learning and memory and other behaviors (Zhuo et al, 1998) has led to investigations suggesting roles for CO in neurological disorders such as stroke and Alzheimer's disease (Schipper, 2004).…”

Section: Endogenous Neurotoxins and The Pathological Second Phase Of mentioning

confidence: 99%

Awareness of Hormesis Will Enhance Future Research in Basic and Applied Neuroscience

Mattson

2008

Critical Reviews in Toxicology

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Hormesis is defined operationally as responses of cells or organisms to an exogenous or intrinsic factor (chemical, temperature, psychological challenge, etc.) in which the factor induces stimulatory or beneficial effects at low doses and inhibitory or adverse effects at high doses. The compendium of articles by Calabrese entitled "Neuroscience and Hormesis" provides a broad range of examples of neurobiological processes and responses to environmental factors that exhibit biphasic dose responses, the signature of hormesis. Nerve cell networks are the "first responders" to environmental challenges-they perceive the challenge and orchestrate coordinated adaptive responses that typically involve autonomic, neuroendocrine, and behavioral changes. In addition to direct adaptive responses of neurons to environmental stressors, cells subjected to a stressor produce and release molecules such as growth factors, cytokines, and hormones that alert adjacent and even distant cells to impending danger. The discoveries that some molecules (e.g., carbon monoxide and nitric oxide) and elements (e.g., selenium and iron) that are toxic at high doses play fundamental roles in cellular signaling or metabolism suggest that during evolution, organisms (and their nervous systems) coopted environmental toxins and used them to their advantage. Neurons also respond adaptively to everyday stressors, including physical exercise, cognitive challenges, and dietary energy restriction, each of which activates pathways linked to the production of neurotrophic factors and cellular stress resistance proteins. The development of interventions that activate hormetic signaling pathways in neurons is a promising new approach for the preventation and treatment of a range of neurological disorders. COMMENTARY ON NEUROSCIENCE AND HORMESISThe biphasic nature of responses to neurotransmitters, neurotrophic factors, cytokines, drugs of abuse, and treatments for a range of neurological disorders is underappreciated and often ignored in basic and applied neuroscience research. Calabrese demonstrates a broad understanding of basic principles of neuroscience, to which he applies his expertise in toxicology and hormesis to catalog hundreds of examples of "toxins," pharmacological agents, intrinsic signaling molecules, and behavioral factors that exhibit biphasic dose responses. The focus throughout the series of articles in "Neuroscience and Hormesis" is on the results of cell culture and in vivo experiments in which the effects of increasing doses of exogenous agents (toxins, neurotransmitters, peptide, hormones, drugs of abuse, etc.) on neuronal survival or plasticity or on animal behavior has been investigated. Calabrese aptly explores the existence of hormesis in most of the major areas of the field of neuroscience, ranging from developmental mechanisms (cell survival and neurite outgrowth) to synaptic plasticity to behavior to

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Heme oxygenase expression in human central nervous system disorders

Cited by 227 publications

References 117 publications

Cerebroprotective Functions of HO-2

Cerebroprotective Functions of HO-2

Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinases

Awareness of Hormesis Will Enhance Future Research in Basic and Applied Neuroscience

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