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Calpain

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https://www.readbyqxmd.com/read/28432466/calpain-inhibition-prevents-flotillin-re-ordering-and-src-family-activation-during-capacitation
#1
Deneb Maldonado-García, Monica L Salgado-Lucio, Ana L Roa-Espitia, Tania Reyes-Miguel, Enrique O Hernández-González
Prior to fertilization, mammalian sperm undergo several molecular, biochemical and physiological changes in a process termed capacitation. However, the mechanisms explaining the involvement of cytoskeletal remodeling and membrane re-ordering in each process prior to fertilization remain poorly understood. We found that the migration of both flotillin microdomains and Src family kinases towards the apical ridge of guinea pig sperm occurs under capacitating conditions. This re-ordering is associated with spectrin cleavage by calpain...
April 22, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28432377/emerging-roles-of-calpain-proteolytic-systems-in-macrophage-cholesterol-handling
#2
REVIEW
Takuro Miyazaki, Akira Miyazaki
Calpains are Ca(2+)-dependent intracellular proteases that play central roles in the post-translational processing of functional proteins. In mammals, calpain proteolytic systems comprise the endogenous inhibitor calpastatin as well as 15 homologues of the catalytic subunits and two homologues of the regulatory subunits. Recent pharmacological and gene targeting studies in experimental animal models have revealed the contribution of conventional calpains, which consist of the calpain-1 and -2 isozymes, to atherosclerotic diseases...
April 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28431398/decreased-calpain-activity-in-chronic-myeloid-leukemia-impairs-apoptosis-by-increasing-survivin-in-myeloid-progenitors-and-xiap1-in-differentiating-granulocytes
#3
Weiqi Huang, Ling Bei, Elizabeth E Hjort, Elizabeth A Eklund
Chronic Myeloid Leukemia (CML) is characterized by translocations between chromosomes 9 and 22, resulting in expression of Bcr-abl oncogenes. Although the clinical course of CML was revolutionized by development of Bcr-abl-directed tyrosine kinase inhibitors (TKIs), CML is not cured by these agents. Specifically, the majority of subjects relapsed in clinical trials attempting TKI discontinuation, suggesting persistence of leukemia stem cells (LSCs) even in molecular remission. Identifying mechanisms of CML-LSC persistence may suggest rationale therapeutic targets to augment TKI efficacy and lead to cure...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429669/what-can-pharmacological-models-of-retinal-degeneration-tell-us
#4
M H Reisenhofer, J Balmer, V Enzmann
Animal models with pharmacologically induced retinal degeneration including sodium iodate (NaIO3) and N-methyl-N-nitrosourea (MNU) have been extensively used in ophthalmic research to investigate retinal degeneration. NaIO3 induces degeneration of the retinal pigment epithelium (RPE) followed by photoreceptor (PRC) cell death, mimicking features of age-related macular degeneration. In contrast, MNU leads to rapid destruction of the PRCs only, enabling the use of the MNU model to investigate degeneration induced in retinitis pigmentosa...
March 31, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28428352/thrombin-mediated-degradation-of-human-cardiac-troponin-t
#5
Ivan A Katrukha, Alexander E Kogan, Alexandra V Vylegzhanina, Marina V Serebryakova, Ekaterina V Koshkina, Anastasia V Bereznikova, Alexey G Katrukha
BACKGROUND: Cardiac troponin T (cTnT) is an acknowledged biomarker of acute myocardial infarction (AMI) that is known to be prone to proteolytic degradation in serum. Such degradation is usually explained by the action of μ -calpain, although there could be other candidates for that role. In the current study, we explored the hypothesis that thrombin-mediated cTnT cleavage occurs as a result of the serum sample preparation. METHODS: cTnT degradation was studied by using immunoblotting and mass spectrometry (MS) analysis...
April 20, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28427998/nitric-oxide-regulated-proteolysis-of-human-cyp2b6-via-the-ubiquitin-proteasome-system
#6
Choon-Myung Lee, Shweta Tripathi, Edward T Morgan
We showed previously that rat cytochrome P450 CYP2B1 undergoes NO-dependent proteasomal degradation in response to inflammatory stimuli, and that the related human enzyme CYP2B6 is also down-regulated by NO in primary human hepatocytes. To investigate the mechanism of CYP2B6 down-regulation, we made several cell lines (HeLa and HuH7 cells) in which native CYP2B6 or CYP2B6 with a C-terminal V5 tag (CYP2B6V5) are expressed from a lentiviral vector with a cytomegalovirus promoter. Native CYP2B6 protein was rapidly down-regulated in HeLa cells within 3h of treatment with the NO donor (Z)-1-[2-(2-Aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, while its mRNA level was not down-regulated...
April 17, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28422847/correlation-between-calpain-10-single-nucleotide-polymorphisms-and-obstructive-sleep-apnea-hypopnoea-syndrome-with-ischemic-stroke-in-a-chinese-population-a-population-based-study
#7
Wei Zhang, Zhi-Ru Zhao, Chang-Fei Dai, Rong Zhang, Jie Chen, Hui-Juan Tian, Yun-Long Wang, Ji-Hong Sun, Qiu-Fang Lian
BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common chronic disorder which is followed by various complications. Calpain-10 belongs to a commonly expressed member of the Calpain-like cysteine protease family, which acts as risk marker for some diseases. The purpose of this study is to elucidate correlation between Calpain-10 single-nucleotide polymorphisms (SNPs) and the incidence of OSAHS followed by ischemic stroke (IS). METHODS: OSAHS patients were divided as OSAHS + IS, OSAHS, and control groups, respectively...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28421435/seasonal-changes-in-proteolytic-activity-of-calpains-in-striated-muscles-of-long-tailed-ground-squirrel-spermophilus-undulatus
#8
S S Popova, I M Vikhlyantsev, N M Zakharova, Z A Podlubnaya, E E Fesenko
Seasonal changes in proteolytic activity and content of calpains in striated muscles of the longtailed ground squirrel Spermophilus undulatus were studied by casein zymography and Western blotting analysis. The results testify to hyperactivation of calpain proteases in the skeletal muscles of awakened animals during the "winter" activity. The observed changes are discussed in the context of adaptation of skeletal muscles of long-tailed ground squirrels to hibernation.
January 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28420443/tau-phosphorylation-induced-by-severe-closed-head-traumatic-brain-injury-is-linked-to-the-cellular-prion-protein
#9
Richard Rubenstein, Binggong Chang, Natalia Grinkina, Eleanor Drummond, Peter Davies, Meir Ruditzky, Deep Sharma, Kevin Wang, Thomas Wisniewski
Studies in vivo and in vitro have suggested that the mechanism underlying Alzheimer's disease (AD) neuropathogenesis is initiated by an interaction between the cellular prion protein (PrP(C)) and amyloid-β oligomers (Aβo). This PrP(C)-Aβo complex activates Fyn kinase which, in turn, hyperphosphorylates tau (P-Tau) resulting in synaptic dysfunction, neuronal loss and cognitive deficits. AD transgenic mice lacking PrP(C) accumulate Aβ, but show normal survival and no loss of spatial learning and memory suggesting that PrP(C) functions downstream of Aβo production but upstream of intracellular toxicity within neurons...
April 18, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28419922/cadmium-induces-ca-2-mediated-calpain-1-caspase-3-dependent-apoptosis-in-primary-cultured-rat-proximal-tubular-cells
#10
Hong Wang, Nianhui Zhai, Ying Chen, Haibin Xu, Kehe Huang
Calcium, as a ubiquitous second messenger, governs a large array of cellular processes and is necessary for cell survival. More recently, it was observed that the cytosolic Ca(2+) concentration ([Ca(2+)]c) elevation could induce apoptosis in primary cultured rat proximal tubular (rPT) cells exposed to cadmium (Cd), but the concrete mechanism is still unclear. This study was designed to investigate the signal pathway involved in [Ca(2+)]c elevation-mediated apoptosis. The results confirmed the elevation of [Ca(2+)]c by confocal microscopy and enhancement of the apoptosis by Hoechst 33258 staining and flow cytometer when rPT cells were exposed to Cd for 12h...
April 8, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28418645/brain-region-and-isoform-specific-phosphorylation-alters-kalirin-sh2-domain-interaction-sites-and-calpain-sensitivity
#11
Megan B Miller, Yan Yan, Kazuya Machida, Drew D Kiraly, Aaron D Levy, Yi I Wu, TuKiet T Lam, Thomas Abbott, Anthony J Koleske, Betty A Eipper, Richard E Mains
Kalirin7 (Kal7), a postsynaptic Rho GDP/GTP exchange factor (RhoGEF), plays a crucial role in long-term potentiation and in the effects of cocaine on behavior and spine morphology. The KALRN gene has been linked to schizophrenia and other disorders of synaptic function. Mass spectrometry was used to quantify phosphorylation at 26 sites in Kal7 from individual adult rat nucleus accumbens and prefrontal cortex before and after exposure to acute or chronic cocaine. Region- and isoform-specific phosphorylation was observed along with region-specific effects of cocaine on Kal7 phosphorylation...
April 25, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28400209/astaxanthin-attenuates-glutamate-induced-apoptosis-via-inhibition-of-calcium-influx-and-endoplasmic-reticulum-stress
#12
Xiaotong Lin, Yan Zhao, Shanhe Li
Astaxanthin (AST) is a carotenoid that has been shown to have neuroprotective effects. In this study, it was found that AST significantly inhibited glutamate-induced loss of cell viability and apoptosis. AST pretreatment attenuated glutamate-induced activation of caspase-3, reduction of anti-apoptotic protein Bcl-2, and increase of pro-apoptotic protein Bak. In addition, AST pretreatment suppressed the production of intracellular reactive oxygen species. AST treatment also prevented glutamate-induced increase of the level of activated p38 mitogen-activated protein kinase (MAPK), which has been shown to promote apoptotic events...
April 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28398517/depolarization-causes-the-formation-of-a-ternary-complex-between-glialcam-mlc1-and-clc-2-in-astrocytes-implications-in-megalencephalic-leukoencephalopathy
#13
Sònia Sirisi, Xabier Elorza-Vidal, Tanit Arnedo, Mercedes Armand-Ugón, Gerard Callejo, Xavier Capdevila-Nortes, Tania López-Hernández, Uwe Schulte, Alejandro Barrallo-Gimeno, Virginia Nunes, Xavier Gasull, Raúl Estévez
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy caused by mutations in either MLC1 or GLIALCAM. GlialCAM is necessary for the correct targeting of MLC1, but also for the targeting of the Cl- channel ClC-2. Furthermore, GlialCAM modifies ClC-2 functional properties in vitro. However, in vivo studies in GlialCAM-/- mice have shown that the modification of ClC-2 activity only occurs in oligodendrocytes, despite GlialCAM and ClC-2 being expressed in astrocytes. Thus, the relationship between GlialCAM, MLC1 and ClC-2 in astrocytes is unknown...
April 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28393458/increased-filaggrin-metabolizing-enzyme-activity-in-atopic-skin-a-pilot-study-using-a-canine-model-of-atopic-dermatitis
#14
Natalia Fanton, Domenico Santoro, Luisa Cornegliani, Rosanna Marsella
BACKGROUND: Filaggrin (FLG) and its metabolites are essential for skin barrier function and hydration of the stratum corneum. Alteration of the FLG metabolism could be the basis for an abnormal skin barrier in allergic dogs. OBJECTIVES: To investigate the expression and distribution of calpain-1, caspase-14, furin and matriptase, four enzymes involved in FLG metabolism, in the skin of atopic and healthy beagles. METHODS: Skin biopsies were collected from four healthy and four atopic beagles before and after allergen exposure...
April 9, 2017: Veterinary Dermatology
https://www.readbyqxmd.com/read/28392447/s-nitrosation-of-calpains-is-associated-with-cardioprotection-in-myocardial-i-r-injury
#15
Matthias Totzeck, Sebastian Korste, Ilkka Miinalainen, Ulrike B Hendgen-Cotta, Tienush Rassaf
BACKGROUND: Myocardial infarction remains the single leading cause of death worldwide. Upon reperfusion of occluded arteries, deleterious cellular mediators particularly located at the mitochondria level can be activated, thus limiting the outcome in patients. This may lead to the so-called ischemia/reperfusion (I/R) injury. Calpains are cysteine proteases and mediators of caspase-independent cell death. Recently, they have emerged as central transmitters of cellular injury in several cardiac pathologies e...
April 6, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28386365/calpain-1-regulates-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-human-lung-epithelial-cells-via-pi3k-akt-signaling-pathway
#16
Wei-Jun Tan, Qiu-Yue Tan, Ting Wang, Min Lian, Li Zhang, Zhen-Shun Cheng
Cell proliferation, transformation, and epithelial-mesenchymal transition (EMT) are key processes involved in the development of idiopathic pulmonary fibrosis (IPF). This study investigated the regulatory factors and signaling pathways that mediate EMT in the human type II alveolar epithelial A549 cell line. A549 cells were cultured in RPMI-1640 medium and allocated to the following four groups: blank control group or treated with transforming growth factor-β1 (TGF-β1), TGF-β1 + PD 150606 (a calpain 1 inhibitor), or PD 150606...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28386216/calpastatin-overexpression-preserves-cognitive-function-following-seizures-while-maintaining-post-injury-neurogenesis
#17
Vanessa M Machado, Ana Sofia Lourenço, Cláudia Florindo, Raquel Fernandes, Caetana M Carvalho, Inês M Araújo
In the adult mammalian brain, new neurons continue to be produced throughout life in two main regions in the brain, the subgranular zone (SGZ) in the hippocampus and the subventricular zone in the walls of the lateral ventricles. Neural stem cells (NSCs) proliferate in these niches, and migrate as neuroblasts, to further differentiate in locations where new neurons are needed, either in normal or pathological conditions. However, the endogenous attempt of brain repair is not very efficient. Calpains are proteases known to be involved in neuronal damage and in cell proliferation, migration and differentiation of several cell types, though their effects on neurogenesis are not well known...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28376667/environmental-enrichment-mitigates-deficits-after-repetitive-mild-tbi
#18
Xiaxia Liu, Jianhua Qiu, Sasha Alcon, Jumana Hashim, William Meehan, Rebekah Mannix
While environmental enrichment has been shown to improve functional and histologic outcomes in preclinical moderate-severe traumatic brain injury (TBI), there is a paucity of preclinical data regarding enrichment strategies in the setting of repetitive mild traumatic brain injury (rmTBI). Given the vast numbers of athletes who sustain rmTBI, the mounting evidence of the long-term and progressive sequelae of rmTBI, and the lack of targeted therapies to mitigate these sequelae, successful enrichment interventions in rmTBI could have large public health significance...
April 4, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28372990/neurotoxic-mechanisms-by-which-the-usp14-inhibitor-iu1-depletes-ubiquitinated-proteins-and-tau-in-rat-cerebral-cortical-neurons-relevance-to-alzheimer-s-disease
#19
Magdalena J Kiprowska, Anna Stepanova, Dustin R Todaro, Alexander Galkin, Arthur Haas, Scott M Wilson, Maria E Figueiredo-Pereira
In Alzheimer's disease proteasome activity is reportedly downregulated, thus increasing it could be therapeutically beneficial. The proteasome-associated deubiquitinase USP14 disassembles polyubiquitin-chains, potentially delaying proteasome-dependent protein degradation. We assessed the protective efficacy of inhibiting or downregulating USP14 in rat and mouse (Usp14(axJ)) neuronal cultures treated with prostaglandin J2 (PGJ2). IU1 concentrations (HIU1>25μM) reported by others to inhibit USP14 and be protective in non-neuronal cells, reduced PGJ2-induced Ub-protein accumulation in neurons...
March 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28366876/endothelial-cell-calpain-as-a-critical-modulator-of-angiogenesis
#20
REVIEW
Yixuan Zhang, Norika Mengchia Liu, Yongchen Wang, Jiyoun Youn, Hua Cai
Calpains are a family of calcium-dependent non-lysosomal cysteine proteases. In particular, calpains residing in the endothelial cells play important roles in angiogenesis. It has been shown that calpain activity can be increased in endothelial cells by growth factors, primarily vascular endothelial growth factor (VEGF). VEGF/VEGFR2 induces calpain 2 dependent activation of PI3K/AMPK/Akt/eNOS pathway, and consequent nitric oxide production and physiological angiogenesis. Under pathological conditions such as tumor angiogenesis, endothelial calpains can be activated by hypoxia...
March 30, 2017: Biochimica et Biophysica Acta
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