Hsp27 Associates with Actin and Limits Injury in Energy Depleted Renal Epithelia

Why, Scott K. Van; Mann, A. S.; Ardito, Thomas; Thulin, Gunilla; Ferris, Sarah; Macleod, Megan A.; Kashgarian, Michael; Siegel, Norman J.

doi:10.1097/01.asn.0000038687.24289.83

Cited by 58 publications

(51 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…13 Indeed, stress or injury in renal tubule cells promote association or colocalization of HSP27 with F-actin leading to cytoprotection in vitro. 51,52 We propose that renal overexpression of huA 1 ARs led to increased HSP27 synthesis in the injected kidney with resultant F-actin stabilization with subsequent protection against AKI after liver IR.…”

Section: Discussionmentioning

confidence: 96%

Selective intrarenal human A1 adenosine receptor overexpression reduces acute liver and kidney injury after hepatic ischemia reperfusion in mice

Park

Chen

Kim

et al. 2010

Laboratory Investigation

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 96%

Selective intrarenal human A1 adenosine receptor overexpression reduces acute liver and kidney injury after hepatic ischemia reperfusion in mice

Park

Chen

Kim

et al. 2010

Laboratory Investigation

View full text Add to dashboard Cite

“…Although previous studies have implicated Hsp27 in regulation of actin polymerization, the primary molecular interaction considered was direct binding of Hsp27 to actin subunits (Landry and Huot 1999;Butt et al 2001;Bitar 2002;Van Why et al 2003;Pichon et al 2004;Chaudhuri and Smith 2008) or binding to actin-associated tropomyosin and caldesmon Bitar 2004, 2006). Using purified Hsp27 and actin, in vitro studies have shown that nonphosphorylated Hsp27 inhibits actin polymerization, while phosphorylated Hsp27 permits actin polymerization.…”

Section: Discussionmentioning

confidence: 99%

Thiolutin inhibits endothelial cell adhesion by perturbing Hsp27 interactions with components of the actin and intermediate filament cytoskeleton

Jia

Isenberg

et al. 2010

Cell Stress and Chaperones

View full text Add to dashboard Cite

show abstract

“…Data concerning the cytoprotective effect of HSP induced by heat (8,11,41), injury (3,4,10,12), or transfection (15,18) provides important correlative, but not definitive, evidence of a key role for HSP in modulating acute cellular injury. If increased expression of HSP is protective, then downregulation should augment cellular injury or impair restitution of cellular integrity.…”

Section: Discussionmentioning

confidence: 99%

“…Studies aimed at establishing a causative link between HSP induction and cytoprotection have examined the effects of overexpression of the heat-shock response by means of preconditioning (8 -12), pharmacologic induction (13,14), or transfection (15). Preconditioning requires the application of an initial injury to induce HSP, which confounds the interpretation of outcome.…”

mentioning

confidence: 99%

Differential Inhibition of HSP72 and HSP25 Produces Profound Impairment of Cellular Integrity

Riordan

Garg

Thulin³

et al. 2004

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Abstract. To test a putative cause and effect relationship between heat-shock protein (HSP) expression and response to renal cell injury, HSP72 and HSP25 were differentially inhibited in LLC-PK1 cells by means of transcription factor decoy and short interference RNA (siRNA). Cellular injury was assessed by solubilization of NaK ATPase (S-NaK). An exonuclease-resistant, ethylene glycol-bridged, circular oligonucleotide decoy for heat-shock transcription factor (HSF)-1, based on the sequence of the porcine heat-shock element, was constructed and validated. It was found that under all experimental conditions, cells had comparable ATP levels; that decoy of unligated or scrambled sequence was ineffective; that HSP72 mRNA and HSP72/HSP25 proteins were significantly reduced in decoy-treated cells; and that the dampened response to HSF activation in decoy-treated, injured cells was accompanied by a substantially amplified loss of cellular integrity (S-NaK was 85% compared with baseline levels). Specific inhibition of HSP72 that used siRNA directed against an inducible porcine HSP72 gene resulted in complete ablation of injury-induced HSP72. Isolated inhibition of HSP72 was also associated with marked NaK ATPase detachment from the cytoskeleton (S-NaK was 135% compared with baseline levels). These studies suggest that an HSF-1 decoy effectively dampens the HSP72/HSP25 response to injury in renal cells; that HSP72 siRNA ablates injury-induced induction of HSP72; and that dampening of the HSP72/HSP25 response and ablation of the HSP72 response are both associated with impaired restitution of cellular polarity.In unstressed cells, preformed heat-shock transcription factors (HSF-1 and HSF-2) are inactive in the cytosol (1). HSF-1 is predominantly involved in stress-related responses, whereas HSF-2 appears to be an important developmental regulator. HSF-1 is rapidly released from the constitutively expressed heat-shock protein (HSP) 90 when demand for this chaperone increases as denatured and aggregated proteins accumulate under conditions of cell stress (2). Activated HSF rapidly trimerizes and translocates to the nucleus, where it binds to GAAn repeats that comprise the heat-shock element (HSE). Studies from our laboratory and others have previously demonstrated the activation of HSF-1 by graded reductions in cellular ATP in vivo (3) and in vitro (4 -7). Activation of HSF-1 resulted in the induction of HSP72 and HSP25 after either ATP depletion or ischemic injury (5).The relative importance of HSP72 and HSP25 in the protection or repair of renal epithelial cells exposed to ATP depletion remains unclear. Studies aimed at establishing a causative link between HSP induction and cytoprotection have examined the effects of overexpression of the heat-shock response by means of preconditioning (8 -12), pharmacologic induction (13,14), or transfection (15). Preconditioning requires the application of an initial injury to induce HSP, which confounds the interpretation of outcome. Pharmacologic induction and transfection may alter ba...

show abstract

Hsp27 Associates with Actin and Limits Injury in Energy Depleted Renal Epithelia

Abstract: Abstract. The purpose of the study was to determine whether Hsp27 interacts with actin and could protect against selected manifestations of injury from energy depletion in renal epithelia.

Cited by 58 publications

References 26 publications

Selective intrarenal human A1 adenosine receptor overexpression reduces acute liver and kidney injury after hepatic ischemia reperfusion in mice

Selective intrarenal human A1 adenosine receptor overexpression reduces acute liver and kidney injury after hepatic ischemia reperfusion in mice

Thiolutin inhibits endothelial cell adhesion by perturbing Hsp27 interactions with components of the actin and intermediate filament cytoskeleton

Differential Inhibition of HSP72 and HSP25 Produces Profound Impairment of Cellular Integrity

Contact Info

Product

Resources

About