Heat shock protein-70 repairs proximal tubule structure after renal ischemia

Bidmon, Bettina; Endemann, Michaela; Müller, Thomas; Arbeiter, Klaus; Herkner, Kurt; Aufricht, Christoph

doi:10.1046/j.1523-1755.2000.00423.x

Cited by 61 publications

(68 citation statements)

References 11 publications

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“…In other injury models, overexpression of Hsp70 via transfection before nonlethal injury resulted in significantly faster stabilization of the cytoskeleton during a subsequent recovery period (26,29,31). Here, we could demonstrate for the first time a significant stabilization of cellular integrity in a CD model after transient transfection with Hsp70.…”

Section: Discussionmentioning

confidence: 54%

“…Previous studies from our group in kidney cells and mesothelial cells provide evidence for a distinct cytoprotective role of HSP in various aspects of cytoskeletal disruption and reorganization in epithelial cells after nonlethal injury (26,29,31,32). Sziksz et al (30) reported in-vivo findings which suggest a distinct impact of the Hsp70 protein family in CD.…”

Section: Discussionmentioning

confidence: 63%

“…To provide more direct evidence that Hsp70 is responsible for stabilization of ezrin and E-cadherin in the cytoskeletal fraction of Caco-2 cells during recovery from gliadin exposure, we used an in-vitro repair assay (Figures 3 and 4) as described before (26,31,32). Performing repeat differential Triton extraction of injured cytoskeletal fractions (Pel) results in additional disruption of cytoskeletal associated proteins, which then also shift into the noncytoskeletal fraction (Sup).…”

Section: Resultsmentioning

confidence: 99%

“…Our methodological approach using Triton extraction is now a well-accepted model of analyzing disruption of the cytoskeletal architecture, regarding as a classic marker of sublethal epithelial cell injury (26,31,32). Under normal conditions, marker proteins of cytoskeletal anchorage or associated proteins are found in the cytoskeletal pellet.…”

Section: Discussionmentioning

confidence: 99%

“…This supports the concept that Hsp70 is critical for maintaining cytoskeleton integrity in these cells after exposure to gliadin. To test this concept, we have adapted an in-vitro repair system for analyzing functional interactions between HSP and disrupted elements of the cytoskeleton that was previously established in subcellular fractions of injured renal or mesothelial cells (26,31). This assay is based on the ability of molecular chaperones to bind to hydrophobic sites of denatured proteins and subsequently undergo conformational changes, resulting in refolding, stabilization, and eventually release of reconfirmed proteins (27).…”

Section: Discussionmentioning

confidence: 99%

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Overexpression of Hsp70 confers cytoprotection during gliadin exposure in Caco-2 cells

et al. 2015

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 63%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Overexpression of Hsp70 confers cytoprotection during gliadin exposure in Caco-2 cells

et al. 2015

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Pathophysiology of Acute Kidney Injury

Basile

Anderson

Sutton

2012

Comprehensive Physiology

976

906

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Acute kidney injury (AKI) is the leading cause of nephrology consultation and is associated with high mortality rates. The primary causes of AKI include ischemia, hypoxia or nephrotoxicity. An underlying feature is a rapid decline in GFR usually associated with decreases in renal blood flow. Inflammation represents an important additional component of AKI leading to the extension phase of injury, which may be associated with insensitivity to vasodilator therapy. It is suggested that targeting the extension phase represents an area potential of treatment with the greatest possible impact. The underlying basis of renal injury appears to be impaired energetics of the highly metabolically active nephron segments (i.e., proximal tubules and thick ascending limb) in the renal outer medulla, which can trigger conversion from transient hypoxia to intrinsic renal failure. Injury to kidney cells can be lethal or sublethal. Sublethal injury represents an important component in AKI, as it may profoundly influence GFR and renal blood flow. The nature of the recovery response is mediated by the degree to which sublethal cells can restore normal function and promote regeneration. The successful recovery from AKI depends on the degree to which these repair processes ensue and these may be compromised in elderly or CKD patients. Recent data suggest that AKI represents a potential link to CKD in surviving patients. Finally, earlier diagnosis of AKI represents an important area in treating patients with AKI that has spawned increased awareness of the potential that biomarkers of AKI may play in the future.

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Stress protein flux during recovery from simulated ischemia: Induced heat shock protein 70 confers cytoprotection by suppressing JNK activation and inhibiting apoptotic cell death

Kumar

Tatu

2003

Proteomics

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Multiple stress proteins are recruited in response to stress in living cells. There are limited reports in the literature analyzing multiple stress protein shifts and their functional consequences on stress response. Using two-dimensional electrophoresis we have analyzed shifts in stress protein profiles in response to energy deprivation as a model of ischemic injury to kidneys. A group of chaperones and stress-induced mitogen activated protein (MAP) kinases were analyzed. In addition to examining stress protein induction and phosphorylation we have also examined the mechanism of cytoprotection by heat shock protein 70 (Hsp70). Our results show that, of the different stress proteins examined, only binding protein (BiP) and Hsp70 were significantly induced upon energy deprivation. Other stress proteins, including Hsp27, calnexin, Hsp90 and ERp57 showed alterations in their phosphorylation profiles. Three different MAP kinases, namely p38, extracellular signal regulated kisase and c-jun N-terminal kinase (JNK) were activated in response to energy deprivation. While JNK activation was linked to apoptosis, activated-p38 was involved in phosphorylation of Hsp27. Study of inhibitors of Hsp70 induction or pre-induction of Hsp70 indicated that induced Hsp70 was involved in the suppression of JNK activation thereby inhibiting apoptotic cell death. Our results provide important insights into the flux in stress protein profiles in response to simulated ischemia and highlight the antiapoptotic, cytoprotective mechanism of Hsp70 action.

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Heat shock protein-70 repairs proximal tubule structure after renal ischemia

Abstract: These data support the hypothesis that HSP-70 interacts with cytoskeletal elements during the restoration of proximal tubule cell structure and polarity after renal ischemia. This experimental approach represents a new in vitro assay to study further the role of HSP in cellular repair.

Cited by 61 publications

References 11 publications

Overexpression of Hsp70 confers cytoprotection during gliadin exposure in Caco-2 cells

Overexpression of Hsp70 confers cytoprotection during gliadin exposure in Caco-2 cells

Pathophysiology of Acute Kidney Injury

Stress protein flux during recovery from simulated ischemia: Induced heat shock protein 70 confers cytoprotection by suppressing JNK activation and inhibiting apoptotic cell death

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