Calpains mediate acute renal cell death: role of autolysis and translocation

Liu, Xiuli; Rainey, Juanita J.; Harriman, Jay F.; Schnellmann, Rick G.

doi:10.1152/ajprenal.2001.281.4.f728

Cited by 44 publications

(28 citation statements)

References 47 publications

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“…Another possible mechanism of calpain appearance in urine of anti-GBM nephritic mice is its secretion by tubular epithelial cells. Indeed, as other intracellular enzymes, calpains may leak out from injured and dying cells such as hepatocytes that are exposed to toxic chemicals (22) or tubular epithelial cells that are submitted to hypoxia (23). Our finding that epithelial cells of proximal tubule (HK-2 cells) that were exposed to albumin released calpain in the extracellular milieu supports this hypothesis.…”

Section: Discussionsupporting

confidence: 64%

Calpain Activation and Secretion Promote Glomerular Injury in Experimental Glomerulonephritis

Peltier

Bellocq

Perez

et al. 2006

Journal of the American Society of Nephrology

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Glomerular injury and albuminuria in acute glomerulonephritis are related to the severity of inflammatory process. Calpain, a calcium-activated cysteine protease, has been shown to participate in the development of the inflammatory process. Therefore, for determination of the role of calpain in the pathophysiology of acute glomerulonephritis, transgenic mice that constitutively express high levels of calpastatin, a calpain-specific inhibitor protein, were generated. Wild-type mice that were subjected to anti-glomerular basement membrane nephritis exhibited elevated levels of calpain activity in kidney cortex at the heterologous phase of the disease. This was associated with the appearance in urine of calpain activity, which originated potentially from inflammatory cells, abnormal transglomerular passage of plasma proteins, and tubular secretion. In comparison with nephritic wild-type mice, nephritic calpastatin-transgenic mice exhibited limited activation of calpain in kidney cortex and limited secretion of calpain activity in urine. This was associated with less severe glomerular injury (including capillary thrombi and neutrophil activity) and proteinuria. There was a reduction in NF-B activation, suggesting that calpain may participate in inflammatory lesions through NF-B activation. There also was a reduction in nephrin disappearance from the surface of podocytes, indicating that calpain activity would enhance proteinuria by affecting nephrin expression. Exposure of cultured podocytes to calpain decreased nephrin expression, and, conversely, exposure of these cells to calpastatin prevented TNF-␣ from decreasing nephrin expression, demonstrating a role for the secreted form of calpain. Thus, both activation and secretion of calpains participate in the development of immune glomerular injury.

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Section: Discussionsupporting

confidence: 64%

Calpain Activation and Secretion Promote Glomerular Injury in Experimental Glomerulonephritis

Peltier

Bellocq

Perez

et al. 2006

Journal of the American Society of Nephrology

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“…Renal proximal tubules constitutively express calpains and are activated in response to toxic and hypoxic injuries. Inhibition of calpain activity using various pharmacological agents ameliorated necrotic cell death in prox- imal tubule cells (PTC) subjected to hypoxic injury or ATP depletion (80,130,202,208).…”

Section: Proteasesmentioning

confidence: 99%

Cell death induced by acute renal injury: a perspective on the contributions of apoptosis and necrosis

Padanilam

2003

American Journal of Physiology-Renal Physiology

334

268

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In humans and experimental models of renal ischemia, tubular cells in various nephron segments undergo necrotic and/or apoptotic cell death. Various factors, including nucleotide depletion, electrolyte imbalance, reactive oxygen species, endonucleases, disruption of mitochondrial integrity, and activation of various components of the apoptotic machinery, have been implicated in renal cell vulnerability. Several approaches to limit the injury and augment the regeneration process, including nucleotide repletion, administration of growth factors, reactive oxygen species scavengers, and inhibition of inducers and executioners of cell death, proved to be effective in animal models. Nevertheless, an effective approach to limit or prevent ischemic renal injury in humans remains elusive, primarily because of an incomplete understanding of the mechanisms of cellular injury. Elucidation of cell death pathways in animal models in the setting of renal injury and extrapolation of the findings to humans will aid in the design of potential therapeutic strategies. This review evaluates our understanding of the molecular signaling events in apoptotic and necrotic cell death and the contribution of various molecular components of these pathways to renal injury.

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“…The first group (calpains 1,2,3,8,9,11,12,14), are known as typical calpains because they are comprised of four domains including the Ca 2+ binding domain (domain IV). The second group (calpains 5,6,7,10,13,15) are known as atypical calpains because they lack the Ca 2+ binding domain (domain IV) [1].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial calpain 10 activity and expression in the kidney of multiple species

Giguere¹,

Covington²,

Schnellmann³

2008

Biochemical and Biophysical Research Communications

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Calpains, Ca 2+ -activated cysteine proteases, have been implicated in the progression of multiple disease states. We recently identified calpain 10 as a mitochondrial calpain that is involved in Ca 2+ -induced mitochondrial dysfunction. The goals of this study were to characterize the expression and activity of renal mitochondrial calpain 10 in rabbit, mouse, and rat. Using shRNA technology and immunoblot analysis three previously postulated splice variants of calpain 10 were identified (50, 56, and 75 kDa). SLLVY-AMC zymography and immunoblot analysis was used to directly link calpeptin-sensitive calpain activity to calpain 10 splice variants. Rabbit, mouse, and rat kidney mitochondria contained 75 kDa (calpain 10a), 56 kDa (calpain 10c or 10d), and 50 kDa (calpain 10e). Interestingly, zymography yielded distinct bands of calpain activity containing multiple calpain 10 splice variants in all species. These results provide evidence that several previously postulated splice variants of calpain 10 are localized to the mitochondria in kidneys of rabbits, rats and mice.

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Calpains mediate acute renal cell death: role of autolysis and translocation

Cited by 44 publications

References 47 publications

Calpain Activation and Secretion Promote Glomerular Injury in Experimental Glomerulonephritis

Calpain Activation and Secretion Promote Glomerular Injury in Experimental Glomerulonephritis

Cell death induced by acute renal injury: a perspective on the contributions of apoptosis and necrosis

Mitochondrial calpain 10 activity and expression in the kidney of multiple species

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