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

Mueller, Thomas; Regele, Heinz; Posch, Martin; Marszalek, Martin; Schwarz, Christoph; Pichlhoefer, Bettina; Arbeiter, Klaus; Aufricht, Christoph

doi:10.1097/01.tp.0000128325.48350.be

Cited by 12 publications

(7 citation statements)

References 12 publications

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“…Concerns have been expressed that Hsp70 may be induced following brain stem death, obviating the benefit of therapeutic upregulation. However, Hsp70 has been shown to be only basally expressed in the kidney before engraftment, and hemodynamic instability in donors and the process of organ recovery were not found to produce a measurable increase in Hsp70 (31). This supports a view that therapeutic Hsp70 induction remains potentially beneficial.…”

Section: Discussionmentioning

confidence: 76%

Heat shock protein 90-binding agents protect renal cells from oxidative stress and reduce kidney ischemia-reperfusion injury

Harrison¹,

Sharpe²,

Bellamy³

et al. 2008

American Journal of Physiology-Renal Physiology

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Heat shock proteins (Hsps) are protective in models of transplantation, yet practical strategies to upregulate them remain elusive. The heat shock protein 90-binding agent (HBA) geldanamycin and its analogs (17-AAG and 17-DMAG) are known to upregulate Hsps and confer cellular protection but have not been investigated in a model relevant to transplantation. We examined the ability of HBAs to upregulate Hsp expression and confer protection in renal adenocarcinoma (ACHN) cells in vitro and in a mouse model of kidney ischemia-reperfusion (I/R) injury. Hsp70 gene expression was increased 30-40 times in ACHN cells treated with HBAs, and trimerization and DNA binding of heat shock transcription factor-1 (HSF1) were demonstrated. A three- and twofold increase in Hsp70 and Hsp27 protein expression, respectively, was found in ACHN cells treated with HBAs. HBAs protected ACHN cells from an H2O2-mediated oxidative stress, and HSF1 short interfering RNA was found to abrogate HBA-mediated Hsp induction and protection. In vivo, Hsp70 was upregulated in the kidneys, liver, lungs, and heart of HBA-treated mice. This was associated with a functional and morphological renal protection from I/R injury. Therefore, HBAs mediate upregulation of protective Hsps in mouse kidneys which are associated with reduced I/R injury and may be useful in reducing transplant-associated kidney injury.

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Section: Discussionmentioning

confidence: 76%

Heat shock protein 90-binding agents protect renal cells from oxidative stress and reduce kidney ischemia-reperfusion injury

Harrison¹,

Sharpe²,

Bellamy³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…There are only limited data on HSP in ischemic renal injury in the human system; however, upregulation of HSP-70 expression, mostly upon heat pretreatment, has been shown to confer resistance against subsequent injury in experimental models of ischemia and transplantation [48,59,60]. 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].…”

Section: Hsp In Renal Transplantationmentioning

confidence: 97%

“…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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“…However, this has not been replicated in experimental data, and results from studies are ambiguous and have not shown any definitive protective effects. [24,25] Some studies have even shown unpredictable effects such as enhanced immunogenicity [26] which can be dangerous in a transplant setting.…”

Section: Role Of Hsp In Kidney Transplantationmentioning

confidence: 99%

The role of heat shock proteins in kidney disease

Rao

2016

Journal of Translational Internal Medicine

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Heat Shock Proteins (HSP) belong to the family of intracellular proteins that are constitutively expressed and are upregulated by various stressors including heat, oxidative and chemical stress. HSP helps in reparative processes, including the refolding of damaged proteins and the removal of irreparably damaged proteins that would initiate cellular death or apoptosis. A growing body of evidence has expanded the role of HSP and defined their role in diseases such as neurodegenerative disorders, cancer, ischemic heart disease and kidney diseases. The protective role of HSP in ischemic renal injury has been described and HSP impairment has been noted in other forms of kidney injuries including post-transplant situation. Further research into the role of HSP in prevention of kidney injury is crucial if translation from the laboratory to patient bedside has to occur. This article aims to be a review of heat shock protein, and its relevance to kidney diseases.

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

Cited by 12 publications

References 12 publications

Heat shock protein 90-binding agents protect renal cells from oxidative stress and reduce kidney ischemia-reperfusion injury

Heat shock protein 90-binding agents protect renal cells from oxidative stress and reduce kidney ischemia-reperfusion injury

Heat-shock protein 70: molecular supertool?

The role of heat shock proteins in kidney disease

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