leupeptins and calmidazolium

leupeptins has been researched along with calmidazolium* in 4 studies

Other Studies

4 other study(ies) available for leupeptins and calmidazolium

ArticleYear
Determining time of death: temperature-dependent postmortem changes in calcineurin A, MARCKS, CaMKII, and protein phosphatase 2A in mouse.
    International journal of legal medicine, 2009, Volume: 123, Issue:4

    While the determination of postmortem interval (PMI) is a crucial and fundamental step in any death investigation, the development of appropriate biochemical methods for PMI estimation is still in its infancy. This study focused on the temperature-dependent postmortem degradation of calcineurin A (CnA), calmodulin-dependent kinase II (CaMKII), myristoylated alanine-rich C-kinase substrate (MARCKs), and protein phosphatase 2A (PP2A) in mice. The results show that MARCKS, CaMKII, and the use of lung tissue do not appear to warrant further study for the determination of PMI in humans. In skeletal muscle, CnA underwent a rapid temperature-dependent cleavage (60 --> 57 kDa) over the first 48 h of postmortem interval. At 21 degrees C, this transformation was completed within 24 h. In contrast, PP2A increased within the first 24 h after which it degraded at 21 degrees C but remained stable for up to 96 h at 5 degrees C and 10 degrees C. The 60 --> 57 kDa postmortem conversion of CnA was inhibited by addition of protease inhibitors and MDL-28170 indicating a calpain pathway mediates this breakdown. Proteasome inhibition (MG-132) and calmodulin antagonism (calmidazolium) also inhibited this conversion suggesting that other protein degradation pathways also are in play. In contrast, all of the protease inhibitors and calmidazolium but not ethylene glycol tetraacetic acid led to increased levels of PP2A. The data are discussed in terms of developing a useable field-based biochemical assay for postmortem interval determination in humans and understanding the protein degradation pathways that are initiated upon death.

    Topics: Animals; Blotting, Western; Calcineurin; Calcium; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calpain; Centrifugation; Cysteine Proteinase Inhibitors; Egtazic Acid; Enzyme Inhibitors; Forensic Pathology; Imidazoles; Intracellular Signaling Peptides and Proteins; Leupeptins; Lung; Membrane Proteins; Mice; Muscle, Skeletal; Myristoylated Alanine-Rich C Kinase Substrate; Postmortem Changes; Proteasome Endopeptidase Complex; Protein Phosphatase 2; Temperature

2009
Differential effect of calmodulin antagonists on MG132-induced mitochondrial dysfunction and cell death in PC12 cells.
    Brain research bulletin, 2005, Oct-15, Volume: 67, Issue:3

    Defects in proteasome function have been suggested to be involved in the pathogenesis of neurodegenerative diseases. We examined the effect of calmodulin antagonists on proteasome inhibitor-induced mitochondrial dysfunction and cell viability loss in undifferentiated PC12 cells. Caspase inhibitors (z-IETD.fmk, z-LEHD.fmk and z-DQMD.fmk) and antioxidants attenuated cell death and decrease in GSH contents in PC12 cells treated with 20 microM MG132, a proteasome inhibitor. Calmodulin antagonists (trifluoperazine, W-7 and calmidazolium) had a differential inhibitory effect on the MG132-induced cell death and GSH depletion depending on concentration with a maximal inhibitory effect at 0.5-1 microM. Addition of trifluoperazine and W-7 reduced the MG132-induced nuclear damage, loss of the mitochondrial transmembrane potential followed by cytochrome c release, formation of reactive oxygen species and elevation of intracellular Ca(2+) levels in PC12 cells. Calmodulin antagonists at 5 microM exhibited a cytotoxic effect on PC12 cells but attenuated the cytotoxicity of MG132. The results suggest that the toxicity of MG132 on PC12 cells is mediated by activation of caspase-8, -9 and -3. Trifluoperazine and W-7 at the concentrations of 0.5-1 microM may attenuate the MG132-induced viability loss in PC12 cells by suppressing change in the mitochondrial membrane permeability and by lowering of the intracellular Ca(2+) levels as well as calmodulin inhibition.

    Topics: Animals; Calcium; Calmodulin; Caspase 3; Caspases; Cell Count; Cell Death; Cell Size; Cell Survival; Cytochromes c; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors; Glutathione; Imidazoles; Leupeptins; Mitochondrial Diseases; PC12 Cells; Rats; Reactive Oxygen Species; Sulfonamides; Trifluoperazine

2005
Depolarization regulates cyclin D1 degradation and neuronal apoptosis: a hypothesis about the role of the ubiquitin/proteasome signalling pathway.
    The European journal of neuroscience, 1999, Volume: 11, Issue:2

    Depolarization and subsequent calcium entry exert essential neuroprotective effects but the ultimate effector by which calcium blocks apoptosis is not known. Here we show that inhibition of calcium entry into cerebellar neurons by switching from high to low extracellular K+ concentrations (30-5 mM) induces apoptosis, that correlates with a rapid accumulation of cyclin D1 (CD1), an early marker of the G1/S transition of the cell cycle. These effects on apoptosis and cyclin D1 are mimicked either by blocking calcium entry into neurons (LaCl3, 100 microM or nifedipine, 10(-6) M) or by inhibiting the calcium/calmodulin pathway (calmidazolium, 10(-7) M). The increased CD1 protein levels do not result from a transcriptional upregulation of the CD1 gene by the Ca2+/calmodulin pathway but rather reflect an accumulation due to the lack of degradation by the proteasome-dependent pathway. Specific proteasome antagonists: carbobenzoxyl-leucinyl-leucinyl-norvalinal-H (MG-115), carbobenzoxyl-leucinyl-leucinyl-leucinal-H (MG-132) and clastolactacystin beta-lactone, induce neuronal apoptosis by themselves. Finally, this pathway is functional only at neuroprotective concentrations of K+ (30 mM), suggesting that calcium/CamK signalling pathway may regulate neuronal death by regulating the proteasome-mediated degradation activity of rapidly turning-over proteins (constitutively expressed genes or pre-existing pools of mRNA).

    Topics: Animals; Apoptosis; Calcium; Calmodulin; Cerebellum; Cyclic AMP-Dependent Protein Kinases; Cyclin D1; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; DNA Primers; Enzyme Inhibitors; Gene Expression; Imidazoles; In Situ Nick-End Labeling; Isoquinolines; Leupeptins; Membrane Potentials; Mice; Mice, Inbred Strains; Multienzyme Complexes; Neurons; Potassium Chloride; Protease Inhibitors; Proteasome Endopeptidase Complex; RNA, Messenger; Signal Transduction; Sulfonamides; Ubiquitins

1999
Vasopressin-induced disruption of actin cytoskeletal organization and canalicular function in isolated rat hepatocyte couplets: possible involvement of protein kinase C.
    Hepatology (Baltimore, Md.), 1998, Volume: 28, Issue:4

    The effect of vasopressin (VP) on canalicular function and hepatocellular morphology, with particular regard to actin cytoskeletal organization and the concomitant plasma membrane bleb formation, was studied in isolated rat hepatocyte couplets. VP induced the concentration-dependent formation of multiple plasma membrane blebs as well as simultaneous impairment in both canalicular vacuolar accumulation (cVA) and retention (cVR) of the fluorescent bile acid, cholyl-lysyl-fluorescein (CLF), which evaluate couplet secretory function and tight-junction integrity, respectively. These effects were mimicked by the protein kinase C (PKC) activator, phorbol dibutyrate (PDB), but not by the protein kinase A (PKA) activator, dibutyryl-cAMP. VP-induced bleb formation and canalicular dysfunction were fully prevented by the protein kinase inhibitor, H-7, but not by the PKA inhibitor, KT5720, further suggesting a specific role of PKC. VP-induced alterations were also prevented by pretreatment with the Ca2+-buffering agent, BAPTA/AM, but not with the calmodulin-dependent protein kinase II antagonist, calmidazolium. Neither the Ca2+-activated neutral protease inhibitor, leupeptin, nor the antioxidants, alpha-tocopherol or deferoxamine, were able to prevent either VP-induced plasma membrane blebbing or canalicular dysfunction. The Ca2+-ionophore, A23187, mimicked the VP-induced alterations, but its harmful effects were completely prevented by H-7. Bleb formation induced by VP and PDB was accompanied by an extensive redistribution of filamentous actin from the pericanalicular area to the cell body, and this effect was fully prevented by H-7. These results suggest that VP-induced canalicular and cytoskeletal dysfunction is mediated by PKC and that classical (Ca2+-dependent) PKC appear to be involved because intracellular Ca2+ is required for VP to induce its harmful effects.

    Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Actins; Animals; Antioxidants; Bile Canaliculi; Bucladesine; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases; Carbazoles; Cells, Cultured; Chelating Agents; Cyclic AMP-Dependent Protein Kinases; Cytoskeleton; Egtazic Acid; Enzyme Activation; Enzyme Inhibitors; Imidazoles; Indoles; Leupeptins; Liver; Male; Microscopy, Electron, Scanning; Phorbol 12,13-Dibutyrate; Protein Kinase C; Pyrroles; Rats; Rats, Wistar; Tight Junctions; Vacuoles; Vasopressins

1998
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