Calpastatin overexpression prevents progression of S-1,2-dichlorovinyl-l-cysteine (DCVC)-initiated acute renal injury and renal failure (ARF) in diabetes

Dnyanmote, Ankur V.; Sawant, Sharmilee P.; Lock, Edward A.; Latendresse, John R.; Warbritton, Alan; Mehendale, Harihara M.

doi:10.1016/j.taap.2006.01.018

Cited by 8 publications

(4 citation statements)

References 33 publications

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“…Others have demonstrated that inhibition of calpain activity corrects endothelial dysfunction and penile nitrergic dysfunction in diabetic mice (11). Relevant to organ injury, overexpression of the endogenous calpain inhibitor calpastatin ameliorates renal injury and failure in diabetes (34). Finally, calpain has been implicated in the impaired nerve regenerations of hyperglycemic rats (12).…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia Is a Major Determinant of Albumin Permeability in Diabetic Microcirculation

et al. 2007

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Increased permeability to albumin is a well-known feature of diabetic microvasculature and a negative prognostic factor of vascular complications. The mechanisms responsible for loss of the physiological albumin barrier in diabetic organs remain only partially understood. We have recently demonstrated that the protease -calpain is activated in hyperglycemia, which causes endothelial dysfunction and vascular inflammation. In the present study, we investigated whether -calpain is involved in the hyperpermeability of the diabetic vasculature. We also investigated the mechanistic roles of hyperglycemia and leukocyte adhesion in this process. Albumin permeability in the intact microcirculation of the Zucker diabetic fatty (ZDF) rat was quantified by intravital microscopy. Extravasation of albumin in the microcirculation of ZDF rats was significantly increased when compared with nondiabetic Zucker lean (ZL) rats. Microvascular albumin leakage was prevented by either antisense depletion of -calpain or pharmacological inhibition of calpain in vivo. Calpain inhibition also attenuated urinary albumin excretion in ZDF rats. Glucose concentrations in the range of those found in the blood of ZDF rats increased albumin permeability in nondiabetic ZL rats. Thus, this demonstrates a mechanistic role for hyperglycemia in the hypermeability of diabetes. Depletion of polymorphonuclear leukocytes in vivo failed to prevent glucose-induced hypermeability, which suggests that hyperglycemia can disrupt the physiological endothelial cell barrier of the microcirculation, even in the absence of increased overt leukocyte-endothelium interactions.

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Section: Discussionmentioning

confidence: 99%

Hyperglycemia Is a Major Determinant of Albumin Permeability in Diabetic Microcirculation

et al. 2007

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“…Knockdown strategies utilizing anti-sense RNAs or small interfering RNAs to study the roles of calpains in cell transformation and in other cellular processes have provided significant evidence for non-redundant, distinctive functions for each ubiquitous calpain isoform. Although less widely studied, there is also increasing evidence for the externalization of calpains and their extracellular contribution to tissue damage in response to toxicants or other factors [ 51 - 53 ]. These destructive roles may relate to the documented involvement of calpains in pathways that trigger apoptosis and/or necrosis [ 54 - 59 ] and, discovered most recently, autophagy [ 60 , 61 ].…”

Section: Localization and Functionmentioning

confidence: 99%

The calpains: modular designs and functional diversity

2007

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SummaryThe calpain family is named for the calcium dependence of the papain-like, thiol protease activity of the well-studied ubiquitous vertebrate enzymes calpain-1 (µ-calpain) and calpain-2 (m-calpain).Proteins showing sequence relatedness to the catalytic core domains of these enzymes are included in this ancient and diverse eukaryotic protein family. Calpains are examples of highly modular organization, with several varieties of amino-terminal or carboxy-terminal modules flanking a conserved core. Acquisition of the penta-EF-hand module involved in calcium binding (and the formation of heterodimers for some calpains) seems to be a relatively late event in calpain evolution. Several alternative mechanisms for binding calcium and associating with membranes/phospholipids are found throughout the family. The gene family is expanded in mammals, trypanosomes and ciliates, with up to 26 members in Tetrahymena, for example; in striking contrast to this, only a single calpain gene is present in many other protozoa and in plants. The many isoforms of calpain and their multiple splice variants complicate the discussion and analysis of the family, and challenge researchers to ascertain the relationships between calpain gene sequences, protein isoforms and their distinct or overlapping functions. In mammals and plants it is clear that a calpain plays an essential role in development. There is increasing evidence that ubiquitous calpains participate in a variety of signal transduction pathways and function in important cellular processes of life and death. In contrast to relatively promiscuous degradative proteases, calpains cleave only a restricted set of protein substrates and use complex substraterecognition mechanisms, involving primary and secondary structural features of target proteins. The detailed physiological significance of both proteolytically active calpains and those lacking key catalytic residues requires further study. Gene organization and evolutionary historyThis review focuses on the eukaryotic calpains, although genome databases reveal bacteria, but no archaea, with sequences related to the catalytic core domains (domains dI and dII) of the classical calpains, the criterion used for designating a protein as a calpain. Only single copies of calpain-coding genes are found in the small number of sequenced or partially sequenced protozoan genomes, such as those of the apicomplexan parasites Plasmodium falciparum, Theileria annulata and Cryptosporidium parvum [1][2][3], and of the amitochondrial parasite Entamoeba histolytica [4]. No calpain-like sequences were identified in the human pathogen Giardia lamblia, a diplomonad often considered to be the most basal eukaryotic organism [5]. Protozoan calpains lack a domain containing EF-hand-type Ca 2+ -binding sites, as also do plant and fungal calpains, and thus it seems likely that the proposed cysteine proteasecalmodulin gene fusion leading to the classical calpain structure (for earlier reviews see [6][7][8]) occurred exclusively within the animal lineage....

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“…Experimental models of diverse neuropathological conditions performed in transgenic mice overexpressing calpastatin have been useful for clarifying the role of the calpain system in brain injury and degeneration [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Calpain-induced Proteolysis After Transient Global Cerebral Ischemia and Ischemic Tolerance in a Rat Model

et al. 2006

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The activation of the [Ca(2+)]-dependent cysteine protease calpain plays an important role in ischemic injury. Here, the levels of two calpain-specific substrates, p35 protein and eukaryotic initiation factor 4G (eIF4G), as well as its physiological regulator calpastatin, were investigated in a rat model of transient global cerebral ischemia with or without ischemic tolerance (IT). Extracts of the cerebral cortex, whole hippocampus and hippocampal subregions after 30 min of ischemia and different reperfusion times (30 min and 4 h) were used. In rats without IT, the p35 levels slightly decreased after ischemia or reperfusion, whereas the levels of p25 (the truncated form of p35) were much higher than those in sham control rats after ischemia and remained elevated during reperfusion. The eIF4G levels deeply diminished after reperfusion and the decrease was significantly greater in CA1 and the rest of the hippocampus than in the cortex. By contrast, the calpastatin levels did not significantly decrease during ischemia or early reperfusion, but were upregulated after 4 h of reperfusion in the cortex. Although IT did not promote significant changes in p35 and p25 levels, it induced a slight increase in calpastatin and eIF4G levels in the hippocampal subregions after 4 h of reperfusion.

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Calpastatin overexpression prevents progression of S-1,2-dichlorovinyl-l-cysteine (DCVC)-initiated acute renal injury and renal failure (ARF) in diabetes

Cited by 8 publications

References 33 publications

Hyperglycemia Is a Major Determinant of Albumin Permeability in Diabetic Microcirculation

Hyperglycemia Is a Major Determinant of Albumin Permeability in Diabetic Microcirculation

The calpains: modular designs and functional diversity

Calpain-induced Proteolysis After Transient Global Cerebral Ischemia and Ischemic Tolerance in a Rat Model

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