Enhanced development of caspase-independent cortical cell death during cold storage in kidneys of non-heart-beating donors1

Bellemare, Sarah; Vigneault, Normand; Madore, François; Raymond, Marc André; Cailhier, Jean François; Hébert, Marie Josèe

doi:10.1097/00007890-200206150-00009

Cited by 11 publications

(9 citation statements)

References 35 publications

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“…A recent clinical study compared the renal tubular expression of HSP-70 in donor kidneys to the subsequent clinical course [61]. Interestingly, HSP-70 expression was low regardless of pretransplant insults and posttransplant outcome [61,62]. After engraftment HSP-70 was detectable in the first urine produced by renal grafts in the immediate postoperative period [63].…”

Section: Hsp In Renal Transplantationmentioning

confidence: 99%

Heat-shock protein 70: molecular supertool?

Aufricht

2005

Pediatr Nephrol

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The cellular stress response decreases cellular injury, either via primary induction of cytoresistance or by secondary enhancement of cellular repair mechanisms. The most frequently studied and best understood effectors of the cellular stress response are the heat shock proteins (HSP). HSP are among the oldest tools in the cellular protein machinery, demonstrating extremely high conservation of the genetic code since bacteria. Molecular chaperons, with the HSP-70 being the prototype, cooperate in transport and folding of proteins, preventing aggregation, and even resolubilizing injured proteins. Increasing evidence supports a role for HSP during the recovery from renal ischemia, in particular in cellular salvage from apoptotic cell death and cytoskeletal restoration. Recent studies also report the potential for biomolecular profiling of newborns for the risk of acute renal failure. In peritoneal dialysis novel data suggest the use of HSP expression for biocompatibility testing. More importantly, HSP are prime therapeutic candidates for clinical situations associated with predictable insults, such as organ procurement in transplant medicine and repetitive exposure to hyperosmolar and acidotic peritoneal dialysis fluids. The next challenge will be to define the regulatory pathways of the cellular stress response in these models to introduce novel therapeutic interventions, such as new pharmaceutics enhancing the HSP expression.

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Section: Hsp In Renal Transplantationmentioning

confidence: 99%

Heat-shock protein 70: molecular supertool?

Aufricht

2005

Pediatr Nephrol

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“…Another group of investigators examined the effect of caspase inhibition in kidney cold ischemia [123]. They developed a model of non-heartbeating donors in rats in which cardiac arrest was produced in the rat for 10 minutes prior to perfusion and harvest of kidneys.…”

Section: Pancaspase Inhibitionmentioning

confidence: 99%

Caspases as Drug Targets in Ischemic Organ Injury

Faubel¹,

Edelstein²

2005

curr drug targets immune endocr metabol disord

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Caspases are intracellular cysteine proteases that mediate cell death and inflammation. Caspase-3 is a major mediator of both apoptotic and necrotic cell death. Caspase-1 mediates inflammation though the activation of the cytokines interleukin-1beta (IL-1beta) and interleukin-18 (IL-18). Increases in both caspase-1 and -3 have been described in ischemic injury to various organs including brain, heart and kidney. Both pharmacological inhibitors and genetic approaches have been used to inhibit caspases in vivo. Pancaspase inhibitors protect against ischemic injury in brain, heart and kidney. Pancaspase inhibition also reduces cold preservation injury due to apoptosis in liver endothelial cells and prolongs animal survival after orthotopic liver transplantation. Caspase-1 inhibition or caspase-1 deficiency protects against ischemic injury in brain, heart and kidney models of ischemia. Specifically, impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure. This review focuses on studies of caspase-1 and pancaspase inhibition in ischemic injury to brain, heart and kidney. In addition, the studies of pancaspase inhibition in cold ischemic injury and organ preservation will be reviewed. The therapeutic potential of caspase inhibition in ischemic injury will be discussed.

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“…However, recent experimental data suggest that, despite significant induction at the time of harvest, subsequent HSP-72 expression may be prevented or degraded by cold storage (8). Alternatively, our results suggest that the hemodynamic instability in donors and the insults during the procurement phase were not severe enough to produce an in vivo renal stress response that was measurable by HSP-72 expression at the time of engraftment.…”

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confidence: 62%

HSP-72 Expression in Pre-Transplant Donor Kidney Biopsies and Post-Transplant Outcome

et al. 2004

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In experimental transplant models, upregulation of renal heat shock proteins (HSP) represents a new therapeutic tool to improve allograft survival. In this clinical study, we hypothesized that HSP-72 expression in pretransplant donor kidney biopsies predicts posttransplant outcome. Expression of HSP-72 in pretransplant biopsies was assessed by immunohistochemistry and in situ hybridization in 82 consecutive renal transplantations and clinical data were collected prospectively during the first six months posttransplant. Renal tubular expression of HSP-72 was low and not influenced by donor-, graft-, or procedure-related risk factors. Neither strength nor pattern of pretransplant HSP-72 staining discriminated allografts with complicated (40%) posttransplant courses from those without complications (60%). The low HSP-72 expression in pretransplant donor kidney biopsies failed to predict delayed graft function or acute rejection. These findings suggest that constitutive HSP-72 gene expression at the time of engraftment does not play a role in graft protection.

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Enhanced development of caspase-independent cortical cell death during cold storage in kidneys of non-heart-beating donors1

Cited by 11 publications

References 35 publications

Heat-shock protein 70: molecular supertool?

Heat-shock protein 70: molecular supertool?

Caspases as Drug Targets in Ischemic Organ Injury

HSP-72 Expression in Pre-Transplant Donor Kidney Biopsies and Post-Transplant Outcome

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