Over-expression of heat shock protein 70 protects neuronal cells against both thermal and ischaemic stress but with different efficiencies

Amin, Vaksha; Cumming, D. V. E.; Latchman, David S.

doi:10.1016/0304-3940(96)12421-6

Cited by 102 publications

(52 citation statements)

References 19 publications

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“…3218 combined oxygen-glucose deprivation, and H2O2 exposure (Papadopoulos et al, 1996;Xu and Giffard, 1997). Overexpression of Hsp70 in cultured neurons is also associated with protection (Amin et al, 1996;Beaucamp et al, 1998;Fink et al, 1997;Uney et al, 1993), and overexpression of Hsp70 in astrocytes was found to protect cocultured wild type neurons (Xu et al, 1999). These in vitro injury models mimic some of the aspects of injury involved in ischemic damage during stroke and suggest several ways in which Hsp70 could provide protection.…”

Section: Discussionmentioning

confidence: 87%

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

Giffard

Zhao

et al. 2004

Journal of Experimental Biology

187

127

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SUMMARY Chaperones, especially the stress inducible Hsp70, have been studied for their potential to protect the brain from ischemic injury. While they protect from both global and focal ischemia in vivo and cell culture models of ischemia/reperfusion injury in vitro, the mechanism of protection is not well understood. Protein aggregation is part of the etiology of chronic neurodegenerative diseases such as Huntington's and Alzheimer's, and recent data demonstrate protein aggregates in animal models of stroke. We now demonstrate that overexpression of Hsp70 in hippocampal CA1 neurons reduces evidence of protein aggregation under conditions where neuronal survival is increased. We have also demonstrated protection by the cochaperone Hdj-2 in vitro and demonstrated that this is associated with reduced protein aggregation identified by ubiquitin immunostaining. Hdj-2 can prevent protein aggregate formation by itself, but can only facilitate protein folding in conjunction with Hsp70. Pharmacological induction of Hsp70 was found to reduce both apoptotic and necrotic astrocyte death induced by glucose deprivation or oxygen glucose deprivation. Protection from ischemia and ischemia-like injury by chaperones thus involves at least anti-apoptotic,anti-necrotic and anti-protein aggregation mechanisms.

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Section: Discussionmentioning

confidence: 87%

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

Giffard

Zhao

et al. 2004

Journal of Experimental Biology

187

127

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“…For example, they can act as molecular chaperones during protein synthesis, may be involved in protein transport within the cytoplasm and have been shown to play a role in those processes in which protein folding and refolding are required (Mayer and Brown, 1994). When hsps are upregulated in response to stress they are thought to be able to protect cells by reorganizing damaged proteins and restoring their activities (Li et al, 1993;Yenari et al, 1998;Amin et al, 1996). Consistent with this possibility is the observation that mild heat or ischaemic stress, which is sufficient to induce an upregulation in hsp expression, can protect cells during subsequent exposure to more stressful insults.…”

Section: Introduction Hmentioning

confidence: 90%

The Effect of Neonatal Nerve Injury on the Expression of Heat Shock Proteins in Developing Rat Motoneurones

Kalmár¹,

Burnstock

Vrbová

et al. 2002

Journal of Neurotrauma

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The expression of the heat shock proteins hsp27 and hsp70 was examined in the spinal cord and sciatic nerves of developing rats. Using immunohistochemistry, we found that hsp27 is present in many motoneurones at birth. With development, the intensity of staining increases, reaching adult levels by 21 days, when all sciatic motoneurones express hsp27. In the sciatic nerve, hsp27 is strongly expressed throughout postnatal development. In contrast, hsp70 immunoreactivity in motoneurones and the sciatic nerve is weak at birth and does not change with development. The expression of heat shock proteins has been shown to increase in cells under conditions of stress, where they have beneficial effects on cell survival. The effect of neonatal nerve injury on hsp27 and hsp70 expression was also examined in this study. Four days after injury, staining for hsp27 increases in motoneurones, whereas hsp70 does not change. However, there is a significant increase in hsp70 staining in glial cells surrounding the injured motor pool, predominantly in astrocytes. Since neonatal nerve injury induces apoptotic motoneurone death, we also studied the co-expression of hsp27 with markers of apoptosis. No hsp27-positive motoneurones were found to be apoptotic, as assessed by both TUNEL and caspase-3 immunoreactivity. Therefore, it is possible that the upregulation of hsp27 observed in injured motoneurones may play a role in protecting motoneurones from apoptotic cell death following nerve injury.

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“…24 -26 The heat shock response has been demonstrated to protect a variety of cells, including renal tubular cells, from ischemic injury. 3,15,16,27 This response is mediated, in part, through the production of heat shock proteins such as HSP72; however, the mechanisms by which heat shock and HSP72 exert a cytoprotective effect in the kidney are unclear. In nonrenal cells, the heat shock response and HSP70 have been demonstrated to inhibit cytokine-mediated NF-B activation and inflammatory mediator production.…”

Section: Discussionmentioning

confidence: 99%

Liposomal Delivery of Heat Shock Protein 72 Into Renal Tubular Cells Blocks Nuclear Factor-κB Activation, Tumor Necrosis Factor-α Production, and Subsequent Ischemia-Induced Apoptosis

Meldrum

Burnett

Meng

et al. 2003

Circulation Research

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Abstract-Heat shock protein 72 (HSP72) is a stress-inducible protein capable of protecting a variety of cells from toxins, thermal stress, and ischemic injury. The cytoprotective role and mechanism of action of HSP72 in renal cell ischemic injury remain unclear. To study this, HSP72 was introduced (liposomal transfer) or induced (thermal stress, 43°Cϫ1 hour) in renal tubular cells (LLC-PK1) with Western blot confirmation. Cells were subjected to simulated ischemia 24 hours after liposomal HSP72 transfer or thermal stress, and the effect of HSP72 on nuclear factor-B (NF-B) activation (electrophoretic mobility shift assay and immunohistochemistry), IB␣ production (Western blot), postischemic tumor necrosis factor-␣ (TNF-␣) production (RT-PCR), and apoptosis (TUNEL assay) were determined. In separate experiments, the role of TNF-␣ in apoptosis was determined (anti-TNF-␣ neutralizing antibody). Results demonstrated that both liposomal transfer of HSP72 and thermal induction of HSP72 prevented NF-B activation and translocation, TNF-␣ gene transcription, and subsequent ischemia-induced renal tubular cell apoptosis. Furthermore, TNF-␣ neutralization also inhibited ischemia-induced renal tubular cell apoptosis. These results indicate that liposomal delivery of HSP72 inhibits ischemia-induced renal tubular cell apoptosis by preventing NF-B activation and subsequent TNF-␣ production. Further elucidation of the mechanisms of HSP-induced cytoprotection may result in therapeutic strategies that limit or prevent ischemia-induced renal damage.

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Over-expression of heat shock protein 70 protects neuronal cells against both thermal and ischaemic stress but with different efficiencies

Cited by 102 publications

References 19 publications

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

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

The Effect of Neonatal Nerve Injury on the Expression of Heat Shock Proteins in Developing Rat Motoneurones

Liposomal Delivery of Heat Shock Protein 72 Into Renal Tubular Cells Blocks Nuclear Factor-κB Activation, Tumor Necrosis Factor-α Production, and Subsequent Ischemia-Induced Apoptosis

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