Chaperones, protein aggregation, and brain protection from hypoxic/ischemic injury

Giffard, Rona G.; Xu, Lijun; Zhao, Heng; Carrico, Whitney; Ouyang, Yi‐Bing; Qiao, Yanli; Sapolsky, Robert M.; Steinberg, Gary K.; Hu, Bingren; Yenari, Midori A.

doi:10.1242/jeb.01034

Cited by 184 publications

(143 citation statements)

References 56 publications

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“…In the surf clam Donax variabilis, hyperoxia induced the expression of Hsp70, whereas sulfide-induced oxidative damage induced the expression of sHSPs (Joyner-Matos et al, 2006). Hsp70 and Hsp27 have potential roles against cellular damage induced by oxidative stress Giffard et al, 2004;Huot et al, 1995;Mehlen et al, 1995), Hsp70 probably by acting as a molecular chaperone, whereas the protective effects of sHSPs were related to Z. Arad and others Hsp level (% change from aestivation) Fig.4. The change in small HSP levels after arousal in the foot, kidney and hepatopancreas tissues of S. zonata and S. cariosa.…”

Section: Hsps and Oxidative Stressmentioning

confidence: 94%

Natural annual cycle of heat shock protein expression in land snails: desertversusMediterranean species ofSphincterochila

Arad

Mizrahi

Goldenberg

et al. 2010

Journal of Experimental Biology

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SUMMARYLand snails are subject to daily and seasonal variations in temperature and in water availability, and have evolved annual cycles of activity and aestivation as part of their survival strategy. We tested in the field whether adaptation to different habitats affects the endogenous levels of heat shock proteins (HSPs) in two closely related Sphincterochila snail species, a desiccation-resistant desert species, Sphincterochila zonata, and a Mediterranean-type, desiccation-sensitive species, S. cariosa. We examined HSP levels in various tissues of snails during aestivation and after resumption of activity. Our study shows that, during aestivation, S. cariosa had higher standing stocks of Hsp70 in the foot and the hepatopancreas, and of small HSPs (sHSPs) in all the examined tissues, whereas S. zonata had higher stocks of Hsp70 in the kidney and of Hsp90 in the kidney and in the hepatopancreas. Arousal induced a general upregulation of HSPs, except for Hsp90, the expression of which in the foot was higher during aestivation. We suggest that the stress protein machinery is upregulated during arousal in anticipation of possible oxidative stress ensuing from the accelerating metabolic rate and the exit from the deep hypometabolic state. Our findings support the concept that, in land snails, aestivation and activity represent two distinct physiological states, and suggest that land snails use HSPs as important components of the aestivation mechanism, and as part of their survival strategy during and after arousal. Our study also indicates that adaptation to different habitats results in the development of distinct strategies of HSP expression with likely consequences for the ecology and distribution of land snails. Supplementary material available online at

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Section: Hsps and Oxidative Stressmentioning

confidence: 94%

Natural annual cycle of heat shock protein expression in land snails: desertversusMediterranean species ofSphincterochila

Arad

Mizrahi

Goldenberg

et al. 2010

Journal of Experimental Biology

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“…Biochemical characterization of the Ub-immunoreactive material from CNS disorders is an area of active research. As in many chronic neurodegenerative diseases, HSPs co-localize with Ub-proteins in the inclusions after ischemic injury (Domorakova et al, 2004;Giffard et al, 2004;Hu et al, 2000Hu et al, , 2001Kumar et al, 2003;Liu et al, 2004). Not surprisingly, the expression of HSP 70 is increased after ischemia in vivo and in vitro, and these protein aggregates are rich in chaperones (Aoki et al, 1993;Chen et al, 1996;Currie et al, 2000;Mailhos et al, 1994;Rajdev et al, 2000;Tsuchiya et al, 2003a, b).…”

Section: The Ubiquitin Proteasome System Plays a Key Role In Ischemicmentioning

confidence: 99%

Killer Proteases and Little Strokes—How the Things that do not Kill You Make You Stronger

O’Duffy

Bordelon

McLaughlin

2006

J Cereb Blood Flow Metab

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The phenomenon of ischemic preconditioning was initially observed over 20 years ago. The basic tenant is that if stimuli are applied at a subtoxic level, cells upregulate endogenous protective mechanisms to block injury induced by subsequent stress. Since this discovery, many conserved signaling mechanisms that contribute to activation of this potent protective program have been identified in the brain. A clinical correlate of this basic research finding can be found in patients with a history of transient ischemic attack (TIA), who have a decreased morbidity after stroke. In spite of multidisciplinary efforts to design safer, more effective stroke therapies, we have thus far failed to translate our understanding of endogenous protective pathways to treatments for neurodegeneration. This review is designed to provide clinicians and basic scientists with an overview of stress biology after TIA and preconditioning, discuss new therapeutic strategies to target the protein dysfunction that follows ischemic injury, and propose enhanced biochemical profiling to identify individuals at risk of stroke after TIA. We pay particular attention to the unanticipated consequences of overly aggressive intervention after TIA in which we have found that traditional cytotoxic agents such as free radicals and apoptosis associated proteases is essential for neuroprotection and communication in the stressed brain. These data emphasize the importance of understanding the complex interplay between chaperones, apoptotic proteases including caspases, and the proteolytic degradation machinery in adaptation to neurological injury.

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“…Intracellular hsp70 (ihsp70) have not been evaluated in the brains of DKA patients, although elevations might be anticipated (Ouyang et al, 2006). Increased ihsp70 levels serve cytoprotective functions and have been shown to preserve both neuronal and blood-brain barrier function at the time of various insults (Giffard et al, 2004;Lu et al, 2004;Wagner et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Neuroinflammatory response of the choroid plexus epithelium in fatal diabetic ketoacidosis

Hoffman

Casanova

Cudrici

et al. 2007

Experimental and Molecular Pathology

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A systemic inflammatory response (SIR) occurs prior to and during the treatment of severe diabetic ketoacidosis (DKA). IL-1β, TNF-α and C5b-9 are components of SIR and have been speculated to be involved in the clinical brain edema (BE) of DKA. We studied IL-1β, TNF-α, C5b-9, inducible nitric oxide (iNOS), ICAM-1, IL-10 and Hsp70 expression in the brains of two patients who died as the result of clinical BE during the treatment of DKA. IL-1β was strongly expressed in the choroid plexus epithelium (CPE) and ependyma, and to a lesser extent in the hippocampus, caudate, white matter radiation of the pons, molecular layer of the cerebellum and neurons of the cortical gray matter. TNF-α was expressed to a lesser extent than IL-1 β, and only in the CP. C5b-9, previously shown to be deposited on neurons and oligodendrocytes, was found on CPE and ependymal cells. iNOS and ICAM-1 had increased expression in the CPE and ependyma. Hsp70 and IL-10 were also expressed in the CPE of the case with the shorter duration of treatment. Our data demonstrates the presence of a multifaceted neuroinflammatory cytotoxic insult of the CPE, which may play a role in the pathophysiology of the fatal brain edema of DKA.

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Chaperones, protein aggregation, and brain protection from hypoxic/ischemic injury

Cited by 184 publications

References 56 publications

Natural annual cycle of heat shock protein expression in land snails: desertversusMediterranean species ofSphincterochila

Natural annual cycle of heat shock protein expression in land snails: desertversusMediterranean species ofSphincterochila

Killer Proteases and Little Strokes—How the Things that do not Kill You Make You Stronger

Neuroinflammatory response of the choroid plexus epithelium in fatal diabetic ketoacidosis

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