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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Title 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
Author Renshaw, Gillian Mary Claire; Warburton, Joshua; Girjes, Adeep
Journal Name Frontiers in Bioscience
Editor S Tabibzadeh
Year Published 2004
Place of publication USA
Publisher Frontiers in Bioscience
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.
Peer Reviewed Yes
Published Yes
Publisher URI http://www.bioscience.org/
Volume 9
Issue Number Jan
Page from 110
Page to 116
ISSN 1093-9946
Date Accessioned 2005-04-13
Date Available 2009-09-25T04:42:53Z
Language en_AU
Research Centre Griffith Health Institute; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject PRE2009-Animal Physiology-Cell; PRE2009-Science & Technology
URI http://hdl.handle.net/10072/5505
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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