Activation of Mitochondrial Apoptotic Pathways in Human Renal Allografts After Ischemia-Reperfusion Injury

Castaneda, M. Patricia; Swiatecka‐Urban, Agnieszka; Mitsnefes, Mark; Feuerstein, Dianne; Kaskel, Frederick J.; Tellis, Vivian A.; Devarajan, Prasad

doi:10.1097/01.tp.0000069835.95442.9f

Cited by 178 publications

(112 citation statements)

References 23 publications

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“…For example, it has been shown that ischemic injury to the kidney is associated with apoptosis (21,28 -30), upregulation of Fas (21,27,29), and enhanced ankyrin expression (22) in tubular epithelial cells, and Fasdeficient mice are protected from ischemic renal injury (27). In the study presented here, we have shown that in a model of early renal ischemia-reperfusion injury characterized by apoptotic tubule cell death, the expression of both ankyrin and Fas was markedly induced, and the interaction between these molecules remained intact.…”

Section: Discussionmentioning

confidence: 99%

“…We used well established murine models in which the structural and functional consequences of brief periods of renal ischemia have been previously documented (27)(28)(29)(30). Briefly, male Swiss-Webster mice (Taconic Farms, Germantown, NY) weighing 25 to 35 g were housed with a 12:12 h light:dark cycle and were allowed free access to food and water.…”

Section: Mouse Model Of Renal Ischemia-reperfusion Injurymentioning

confidence: 99%

“…Slides were then incubated with secondary antibodies conjugated with either Cy5 (for Fas) or Cy3 (for ankyrin) and visualized with rhodamine or fluorescein filters, respectively. For colocalization of Fas with apoptotic cells, serial sections were subjected to either the TUNEL assay or to immunohistochemistry as described previously (28,29). Visualization with rhodamine filters revealed cells that stained positive for Fas, and examination with fluorescein filters identified TUNEL-positive nuclei in serial sections.…”

Section: Colocalization In Vivomentioning

confidence: 99%

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The Death Domain of Kidney Ankyrin Interacts with Fas and Promotes Fas-Mediated Cell Death in Renal Epithelia

Río¹,

Imam²,

DeLeon³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Ankyrins are a ubiquitously expressed family of conserved proteins that mediate the linkage of integral membrane proteins such as transporters and channels with the underlying cytoskeleton. Ankyrins possess a conserved death domain, the functional significance of which has remained puzzling. In this study, the death domain of AnkG190, the isoform of ankyrin expressed in kidney tubules, was used as bait in a yeast two-hybrid screen to identify interacting partners. One of these interactions was with the proapoptotic molecule Fas. This was confirmed by coimmunoprecipitation, colocalization, and glutathione S-transferase pull-down assays in cultured renal epithelial (MDCK) cells. Site-directed mutagenesis of a conserved arginine (R1496 in AnkG190), previously shown to be critical for the binding of Fas (R234 in Fas) to FADD, abolished the interaction of ankyrin's death domain with Fas. Overexpression of constructs containing ankyrin's death domain promoted Fas-mediated apoptosis in MDCK cells. The linkage between ankyrin and Fas was confirmed in vivo in mouse kidney tubule cells by coimmunoprecipitation and colocalization. In an established mouse model of renal ischemia-reperfusion injury characterized by apoptotic tubule cell death, the expression of both ankyrin and Fas was markedly induced, and the interaction between these molecules remained intact. The results identify a novel tethering interaction between ankyrin and Fas in kidney epithelia and suggest that AnkG190 may play a role as an adapter molecule in renal tubule cell death.Tethering interactions between membrane proteins and the underlying spectrin-based cytoskeleton play key roles in several cellular activities, including organization of plasma membrane domains (1

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Section: Discussionmentioning

confidence: 99%

Section: Mouse Model Of Renal Ischemia-reperfusion Injurymentioning

confidence: 99%

Section: Colocalization In Vivomentioning

confidence: 99%

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The Death Domain of Kidney Ankyrin Interacts with Fas and Promotes Fas-Mediated Cell Death in Renal Epithelia

Río¹,

Imam²,

DeLeon³

et al. 2004

Journal of the American Society of Nephrology

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“…Proximal and distal tubular cells were identified primarily by morphologic criteria, including the presence of a brush border, the cell size, and nuclearcytoplasmic ratio. Lectin histochemistry with Phaseolus vulgaris erythroagglutinin (Sigma, St. Louis, MO) and Arachis hypogaea (AH; Sigma) was used as a confirmatory assay to identify proximal and distal tubules, respectively, as described previously (26,27). Briefly, serial sections were deparaffinized, treated with 1.25% H 2 O 2 in methanol for 30 min, incubated with either Phaseolus vulgaris erythroagglutinin (1 g/ml) or AH (10 g/ml) for 60 min, and developed with diaminobenzidine.…”

Section: Apoptosis Assay In Kidney Biopsy Samplesmentioning

confidence: 99%

Induction of Renal Tubular Cell Apoptosis in Focal Segmental Glomerulosclerosis

Erkan¹,

Garcia²,

Patterson³

et al. 2005

Journal of the American Society of Nephrology

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The hypothesis that apoptosis represents a proximate mechanism by which tubule cells are damaged in FSGS was tested. Thirty kidney biopsy specimens from children with idiopathic early FSGS were studied retrospectively. Unexpected, apoptosis was evident in both proximal and distal tubule cells. There was a significant correlation between the degree of proteinuria and the number of apoptotic cells. Fas protein was detected predominantly in the tubule cells that underwent apoptosis. When compared with patients with other chronic proteinuric states, those with FSGS displayed a proliferation/ apoptosis ratio in favor of proliferation in the glomerulus but dramatically in favor of apoptosis in the tubules. When both proteinuria and apoptosis were included in a stepwise logistic regression procedure, only apoptosis was found to predict independently the development of ESRD. Prolonged incubation of cultured Madin-Darby canine kidney (distal/collecting) cells with albumin also resulted in a dose-and duration-dependent induction of apoptosis and activation of the Fas pathway, lending support to the novel finding of distal tubule cell apoptosis in patients with FSGS. The results indicate that an elevated tubule cell apoptosis rate at the time of initial biopsy represents an independent predictor of progression to ESRD in patients with early FSGS.

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“…Following reperfusion, a complex series of events occur including generation of reactive oxygen and nitrogen species, generation of proinflammatory cytokines, alteration of microvascular activity, inflammation, and eventually tubular cell death (3). Morphological changes of kidney IR injury include effacement and loss of proximal tubule brush border, proximal tubular dilation and distal tubular casts, necrosis, and apoptosis of proximal tubular cells (6,17,39). In addition, rapid accumulation of massive neutrophils and monocyte/macrophages, and fewer leucocytes in the interstitium of injured kidney is another feature of renal IR injury (3,22,25).…”

mentioning

confidence: 99%

Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia-reperfusion-induced kidney injury

Tong

Maimaitiyiming

et al. 2012

American Journal of Physiology-Renal Physiology

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Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia-reperfusion-induced kidney injury. Am J Physiol Renal Physiol 302: F561-F570, 2012. First published December 7, 2011 doi:10.1152/ajprenal.00355.2011.-cGMP-dependent protein kinase (PKG) is a multifunctional protein. Whether PKG plays a role in ischemia-reperfusion-induced kidney injury (IRI) is unknown. In this study, using an in vivo mouse model of renal IRI, we determined the effect of renal IRI on kidney PKG-I levels and also evaluated whether overexpression of PKG-I attenuates renal IRI. Our studies demonstrated that PKG-I levels (mRNA and protein) were significantly decreased in the kidney from mice undergoing renal IRI. Moreover, PKG-I transgenic mice had less renal IRI, showing improved renal function and less tubular damage compared with their wild-type littermates. Transgenic mice in the renal IRI group had decreased tubular cell apoptosis accompanied by decreased caspase 3 levels/ activity and increased Bcl-2 and Bag-1 levels. In addition, transgenic mice undergoing renal IRI demonstrated reduced macrophage infiltration into the kidney and reduced production of inflammatory cytokines. In vitro studies showed that peritoneal macrophages isolated from transgenic mice had decreased migration compared with control macrophages. Taken together, these results suggest that PKG

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Activation of Mitochondrial Apoptotic Pathways in Human Renal Allografts After Ischemia-Reperfusion Injury

Abstract: Ischemia-reperfusion injury in CAD kidney transplants is associated with a duration-dependent increase in tubular cell apoptosis, mediated at least in part by activation of mitochondrial pathways.

Cited by 178 publications

References 23 publications

The Death Domain of Kidney Ankyrin Interacts with Fas and Promotes Fas-Mediated Cell Death in Renal Epithelia

The Death Domain of Kidney Ankyrin Interacts with Fas and Promotes Fas-Mediated Cell Death in Renal Epithelia

Induction of Renal Tubular Cell Apoptosis in Focal Segmental Glomerulosclerosis

Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia-reperfusion-induced kidney injury

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