Calpains: physiological and pathophysiological significance

Сазонтова, Т. Г.; Matskevich, Alexey A.; Arkhipenko, Yuriy V.

doi:10.1016/s0928-4680(99)00015-2

Cited by 16 publications

(18 citation statements)

References 120 publications

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“…Most notably, DEK1 calpain represents the C-terminal domain of a 240-kDa protein that is predicted to be anchored in the plasma membrane by 21 transmembrane segments interrupted by a putative extra cytosolic loop domain (9). A membrane-anchoring domain is unusal for animal calpains, which mostly are cytosolic enzymes that are translocated to the plasma membrane upon activation (42,43). The only known example of an animal calpain with a predicted membrane anchor is the Drosophila calpain CG3692 that has a transmembrane domain structure similar to DEK1 calpain.…”

Section: Discussionmentioning

confidence: 99%

The Calpain Domain of the Maize DEK1 Protein Contains the Conserved Catalytic Triad and Functions as a Cysteine Proteinase

Wang

Barry

Zhao

et al. 2003

Journal of Biological Chemistry

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Development of the aleurone layer of maize grains requires the activity of the Defective kernel 1 (Dek1) gene, encoding a predicted 240-kDa membrane-anchored protein with a C terminus similar to animal calpain domain II&III. Three-dimensional modeling shows that DEK1 domain II contains a conserved calpain catalytic triad and that domain II&III has a predicted structure similar to m-calpain. Recombinant DEK1 domain II&III exhibits activity in the caseinolytic assay in the absence of calcium, although the activity is enhanced by calcium. This is in sharp contrast to animal calpains, which require Ca 2؉ to be active. Bacterially expressed DEK1 domain II does not display caseinolytic activity, suggesting an important role for DEK1 domain III. Mutation of the catalytic Cys residue to Ser leads to a loss of caseinolytic activity of DEK1 domain II&III. Two features of DEK1 calpain may contribute to maintaining the active site triad in an "active" configuration in the absence of Ca 2؉ , both of which are predicted to keep m-calpain domains IIa and IIb apart. First, DEK1 lacks key charged residues in the basic loop of domain II, and secondly, the absence of an acidic loop in domain III, both of which are predicted to be neutralized upon Ca 2؉ binding. The Dek1 transcript is present in all cell types in developing maize endosperm, suggesting that the activity of the DEK1 calpain is regulated at the posttranscription level. The role of DEK1 in aleurone signaling is discussed.In cereal grains, the aleurone layer consists of densely cytoplasmic cells covering the surface of the endosperm, the grain storage tissue that is used for feed, food and industrial raw material (1). Aleurone cells contain a large numbers of protein and oil bodies and are cytologically and biochemically distinct from the storage cells of the underlying starchy endosperm. Upon imbibition of the grain, aleurone cells secrete enzymes that mobilize stored starch and protein reserves for seedling growth (2). The endosperm develops from the central cell after double fertilization through a cellularization process that results in a peripheral layer of aleurone cell initials (3). From genetic evidence, the tumor necrosis factor receptor-like kinase CRINKLY4 (CR4) is implicated in aleurone cell fate specification (4 -7). Based on the identity of the Cr4 gene product, as well as the peripheral position of the aleurone layer, we proposed a model in which the CR4 receptor is activated by a ligand in the periphery of the endosperm (8). Recently, we isolated the defective kernel 1 (dek1) 1 gene, which is also essential for aleurone cell development (9). Homozygous recessive dek1 endosperm initiates aleurone cell fate specification, but fails to maintain aleurone cell fate, resulting in grains that lack aleurone cells (9). Revertant sector analysis has demonstrated that Dek1 function is essential for the maintenance of aleurone cell fate throughout grain development (10, 11). Sequence analysis predicts that the Dek1 gene encodes a 240 kDa protein with 21 membrane spa...

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Section: Discussionmentioning

confidence: 99%

The Calpain Domain of the Maize DEK1 Protein Contains the Conserved Catalytic Triad and Functions as a Cysteine Proteinase

Wang

Barry

Zhao

et al. 2003

Journal of Biological Chemistry

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“…On the other hand release of cytochrome -c produces depletion of ATP stores [6] and lead to necrotic cell death [10]. The transition from reversible to irreversible injury is characterized by the development of severe membrane permeability defects [5], [11] and degradation of membranous proteins [12]. The mode of cell death shifts from apoptotic to necrotic due to use of ATP stores by apoptosis [2].…”

Section: Introductionmentioning

confidence: 99%

“…Calpastatin suppresses conformational changes in calpain molecule during the initial stages of its activation and inhibits binding to its cell membrane and degradation of membrane proteins [12], [14]. The selective inhibition of calpain activity by calpastatin [15] has improved function of heart which were declined as a result of ishaemia and reperfusion.…”

Section: Introductionmentioning

confidence: 99%

Attenuation of Ischaimia Reperfusion Induced Myocardial Cell Injury in Rat Heart by Calpastatin

2016

IJSR

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Myocardial ischaemia reperfusion is associated with activation of intracellular death proteases known as calpains. Isolated rat heart was subjected to 30 min ischaemia followed by reperfusion for 120min. The effect of calpain inhibitor calpastatin in induced myocardial injury assessed in terms of infract size measured macroscopically, release of LDH and CK have been investigated. Agarose gel electrophoresis was used to assess the DNA fragmentation. TUNEL staining was done to investigate the apoptotic index. Calpastatin has attenuated ischaemia reperfusion induced increase in LDH,CK, myocardial infarct size ,DNA smearing and apoptotic index. It may be concluded that inhibition of intracellular death proteases prevented ischaemia reperfusion induced myocardial cell injury in terms of apoptosis and necrosis.

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“…These enzymes are a family of cytosolic cysteine proteases [19] with a very active role, that includes the catalysis of the hydrolysis of a variety of proteins involved in signal transduction and cytoskeletal remodelling, as well as the participation in physiological processes, such as cell cycle regulation and apoptosis. [20] In mammals, the calpain family comprises several tissuespecific isoforms and two ubiquitous isoenzymes: the mcalpain (or calpain I) and the m-calpain (or calpain II), that require micromolar and millimolar amounts, respectively, of Ca(II) for activation. [21] It has been claimed that the over-activation of the calpains causes several pathological disorders, including brain ischemia, multiple sclerosis, Alzheimer×s disease, muscular dystrophy, and other degenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Novel Peptide-Heterocycle Hybrids: Synthesis and Preliminary Studies on Calpain Inhibition

Mann

Chana

Sánchez-Sancho

et al. 2002

Advanced Synthesis & Catalysis

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New peptidic compounds, having peptide chains linked to bi‐ and tricyclic heterocycles (peptide‐heterocycle hybrids), have been synthesized. The heterocyclic components are derivatives of partially reduced isoquinoline and pyrido[1,2‐b]isoquinoline bearing α,β‐unsaturated carbonyl functionalities. The heterocyclic compounds have been used as acylating agents in coupling reactions with short N‐unprotected peptides. Based on our interest on potential calpain inhibitors, we have used short (2–4 amino acids) peptides with hydrophobic amino acids of the two enantiomeric series. We report preliminary studies on the inhibition of calpain, with some compounds having IC50 values in the nanomolar range.

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Calpains: physiological and pathophysiological significance

Cited by 16 publications

References 120 publications

The Calpain Domain of the Maize DEK1 Protein Contains the Conserved Catalytic Triad and Functions as a Cysteine Proteinase

The Calpain Domain of the Maize DEK1 Protein Contains the Conserved Catalytic Triad and Functions as a Cysteine Proteinase

Attenuation of Ischaimia Reperfusion Induced Myocardial Cell Injury in Rat Heart by Calpastatin

Novel Peptide-Heterocycle Hybrids: Synthesis and Preliminary Studies on Calpain Inhibition

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