IMR Press / FBL / Volume 9 / Issue 1 / DOI: 10.2741/1206

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Oxygen sensors and energy sensors act synergistically to achieve a graded alteration in gene expression: consequences for assessing the level of neuroprotection in response to stressors
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1 School of Physiotherapy and Exercise Science, Griffith University, Gold Coast Campus, PMB 50 Gold Coast Mail Centre, 9726 Queensland, Australia
2 Department of Anatomical and Developmental Biology, University of Queensland, St Lucia, 4072 Queensland, Australia
3 Department of Zoology and Entomology, University of Queensland, St Lucia, 4072 Queensland, Australia
Academic Editor:John Leah
Front. Biosci. (Landmark Ed) 2004, 9(1), 110–116; https://doi.org/10.2741/1206
Published: 1 January 2004
(This article belongs to the Special Issue Regulation of gene expression in the brain)
Abstract

Changes in gene expression are associated with switching to an autoprotected phenotype in response to environmental and physiological stress. Ubiquitous molecular chaperones from the heat shock protein (HSP) superfamily confer neuronal protection that can be blocked by antibodies. Recent research has focused on the interactions between the molecular sensors that affect the increased expression of neuroprotective HSPs above constitutive levels. An examination of the conditions under which the expression of heat shock protein 70 (Hsp70) was up regulated in a hypoxia and anoxia tolerant tropical species, the epaulette shark (Hemiscyllium ocellatum), revealed that up-regulation was dependent on exceeding a stimulus threshold for an oxidative stressor. While hypoxic-preconditioning confers neuroprotective changes, there was no increase in the level of Hsp70 indicating that its increased expression was not associated with achieving a neuroprotected state in response to hypoxia in the epaulette shark. Conversely, there was a significant increase in Hsp70 in response to anoxic-preconditioning, highlighting the presence of a stimulus threshold barrier and raising the possibility that, in this species, Hsp70 contributes to the neuroprotective response to extreme crises, such as oxidative stress. Interestingly, there was a synergistic effect of coincident stressors on Hsp70 expression, which was revealed when metabolic stress was superimposed upon oxidative stress. Brain energy charge was significantly lower when adenosine receptor blockade, provided by treatment with aminophylline, was present prior to the final anoxic episode, under these circumstances, the level of Hsp70 induced was significantly higher than in the pair-matched saline treated controls. An understanding of the molecular and metabolic basis for neuroprotective switches, which result in an up-regulation of neuroprotective Hsp70 expression in the brain, is needed so that intervention strategies can be devised to manage CNS pathologies and minimise damage caused by ischemia and trauma. In addition, the current findings indicate that measurements of HSP expression per se may provide a useful correlate of the level of neuroprotection achieved in the switch to an autoprotected phenotype.

Keywords
Neuroprotection
Gene Expression
Hypoxic – preconditioning
Anoxic-preconditioning
Hypoxia Tolerance
Anoxia Tolerance
Review
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