Calpastatin

Inhibitors of polo-like kinase (PLK) are currently being evaluated as anticancer drugs. However, the molecular mechanism of PLK inhibitor-induced cell death is not fully understood. In this study, we found that GW843682X and BI2536, two inhibitors of PLK1, significantly induced cell death in multiple type cells. The induction of cell death was related to the preferring expression of PLK1. However, in human umbilical vascular endothelial cells (HUVEC) and human colorectal carcinoma cells, which expressed higher levels of both PLK1 and PLK2, PLK1 inhibitors induced very low levels of cell death...

β-catenin is an important regulator of malignant progression. 17β-Estradiol (E2), an important sex hormone in women, promotes the growth and metastasis of triple-negative breast cancer (TNBC). However, whether β-catenin is involved in E2-induced metastasis of TNBC remains unknown. In this study, we show that E2 induces the proliferation, migration, invasion, and metastasis of TNBC cells. E2 induces β-catenin protein expression and nuclear translocation, thereby regulating the expression of target genes such as Cyclin D1 and MMP-9...

BACKGROUND: Diabetes mellitus (DM) is a major risk factor for atrial structural remodeling and atrial fibrillation (AF). Calpain activity is hypothesized to promote atrial remodeling and AF. OBJECTIVE: To investigate the role of calpain in diabetes-associated atrial fibrillation, fibrosis, and calcium handling dysfunction. METHODS: DM-associated AF was induced in wildtype mice and in mice overexpressing the calpain inhibitor calpastatin (CAST-OE) using high-fat diet (HFD) feeding followed by low dose streptozotocin injection (STZ, 75 mg/kg)...

Feed costs and carcass yields affect the profitability and sustainability of sheep production. Therefore, it is crucial to select animals with a higher feed efficiency and high-quality meat production. This study focuses on the impact of dietary and genetic factors on production traits such as feed efficiency, carcass quality, and meat quality. Diets promote optimal sheep growth and development and provide sufficient protein can lead to higher-quality meat. However, establishing an optimized production system requires careful consideration and balance of dietary parameters...

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Reperfusion after ischemia would cause massive myocardial injury, which leads to oxidative stress (OS). Calcium homeostasis imbalance plays an essential role in myocardial OS injury. CaV 1.2 calcium channel mediates calcium influx into cardiomyocytes, and its activity is modulated by a region of calpastatin (CAST) domain L, CSL 54-64. In this study, the effect of Ahf-caltide, derived from CSL 54-64, on myocardial OS injury was investigated. Ahf-caltide decreased the levels of LDH, MDA and ROS and increased heart rate, coronary flow, cell survival and SOD activity during OS...

Beef consumption is expected to increase worldwide, which necessitates the use of Bos indicus cattle that are well-adapted to harsher climates, like the tropics. Yet, beef from these cattle is considered inferior to that of Bos taurus breeds, primarily due to lowered tenderness values and reduced intramuscular fat content. However, the benefits of using Bos indicus genetics are numerous and undeniable. Herein, we explore how decreases in meat quality in these cattle may be offset by increases in livability...

SIGNIFICANCE STATEMENT: Autophagy protects podocytes from injury in diabetic kidney disease (DKD). Restoring glomerular autophagy is a promising approach to limit DKD. This study demonstrates a novel regulatory mechanism of autophagy that blocks this critical protection of the glomerular filtration barrier. We demonstrated that TRPC6 induced in podocytes in mouse models of diabetes mediates calpain activation, thereby impairing podocyte autophagy, causing injury and accelerating DKD. Furthermore, this study provides proof of principle for druggable targets for DKD because restoration of podocyte autophagy by calpain inhibitors effectively limits glomerular destruction...

Hypoxic-ischemic encephalopathy (HIE) is a complex pathophysiological process with multiple links and factors. It involves the interaction of inflammation, oxidative stress, and glucose metabolism, and results in acute and even long-term brain damage and impairment of brain function. Calpain is a family of Ca2+ -dependent cysteine proteases that regulate cellular function. Calpain activation is involved in cerebral ischemic injury, and this involvement is achieved by the interaction among Ca2+ , substrates, organelles, and multiple proteases in the neuronal necrosis and apoptosis pathways after cerebral ischemia...

The objective of this study was to compare the influence of beef production systems using additive combinations of growth-promotant technologies on meat quality. Steer calves ( n  = 120) were assigned to 1 of 4 treatments: 1) no technology (NT; control), 2) antibiotic treated (ANT; NT plus therapeutic antibiotics, monensin, and tylosin), 3) implant treated (IMP; ANT plus a series of three implants), and 4) beta-agonist treated (BA; IMP plus ractopamine-HCl). Muscle biopsy samples from the longissimus lumborum were extracted from a subset ( n  = 4 per treatment) of steers to evaluate expression of calpain-1, calpain-2, and calpastatin using real-time RT-PCR...

The intercalated disk is a cardiac specific structure composed of three main protein complexes-adherens junctions, desmosomes, and gap junctions-that work in concert to provide mechanical stability and electrical synchronization to the heart. Each substructure is regulated through a variety of mechanisms including proteolysis. Calpain proteases, a class of cysteine proteases dependent on calcium for activation, have recently emerged as important regulators of individual intercalated disk components. In this review, we will examine how calcium homeostasis regulates normal calpain function...

This study determined whether castration and electrical stimulation (ES) influenced chevon tenderness and related physiological characteristics in Boer Goat (BG; n = 36; 21 bucks and 15 wethers) and large frame Indigenous Veld Goat (IVG; n = 41; 21 bucks and 20 wethers). Half of buck and wether carcasses were ES (20s, 400 Volts peak, 5 ms pulses at 15 pulses/s) 10 min post-mortem. Dressed carcasses were chilled (4 °C within 1-h post-mortem). pH and temperature decline, % drip loss, sarcomere length (SL), myofibril fragmentation length (MFL; 1- and 4-days post-mortem), Calpain-1, -2 and calpastatin activities (1- and 24-h), Warner-Bratzler shear force (WBSF; 1-day post-mortem) and sensory attributes (tenderness and juiciness; 4-days post-mortem) were measured on Longissimus thoracis et lumborum (LTL) and Semimembranosus (SM) muscles...

BACKGROUND: The family with sequence similarity 20-member C (FAM20C) kinase, a Golgi casein kinase, which is responsible for phosphorylating the majority of the extracellular phosphoproteins within S-x-E/pS motifs, and is fundamentally associated with multiple biological processes to maintain cell proliferation, biomineralization, migration, adhesion, and phosphate homeostasis. In dissecting how FAM20C regulates downstream molecules and potential mechanisms, however, there are multiple target molecules of FAM20C, particularly many phenomena remain elusive, such as changes in cell-autonomous behaviors, incompatibility in genotypes and phenotypes, and others...

The single-nucleotide polymorphism (SNP) form of genes is a valuable source of information regarding their suitability for use as specific markers of desirable traits in beef cattle breeding. For several decades, breeding work focused on improving production efficiency through optimizing the feed conversion ratio and improving daily gains and meat quality. Many research teams previously undertook research work on single-nucleotide polymorphism in myostatin (MSTN), thyroglobulin (TG), calpain (CAPN), and calpastatin (CAST) proteins...

Romosinuano is a tropically adapted Bos taurus breed, and some Mexican breeders aim to improve it genetically. The aim was to estimate allelic and genotypic frequencies for SNPs associated with meat quality in a Mexican Romosinuano population. Four hundred ninety-six animals were genotyped using the Axiom©BovMDv3 array. Only SNPs related to meat quality in this array were studied in this analysis. The Calpain, Calpastatin, and Melanocortin-4 receptor alleles were considered. Allelic and genotypic frequencies and Hardy-Weinberg equilibrium were estimated with the PLINK software...

Cerebral ischemia-reperfusion injury (CIRI) is associated with a poor neurological prognosis in patients who have experienced cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The aim of the current study was to investigate the potential role of a calpain inhibitor in CIRI using a rat model of CA. CA was induced in adult male Sprague-Dawley rats, and MDL28170 (a calpain inhibitor) was administered to the rats within 30 min after the return of spontaneous circulation. Differences between groups were evaluated by measuring survival rate, CPR duration and neurological deficit score...

Tenderness is an important characteristic of meat quality. Calpastatin and calpain play important roles in meat tenderization. However, it is not clear how phosphorylation affects the regulation of calpastatin on μ-calpain and, consequently, meat tenderness. Calpastatin with high and low phosphorylation levels were obtained in vitro corresponding to the treatments by protein kinase A (PKA) and alkaline phosphatase. Then, calpain was incubated with calpastatin with different phosphorylation levels, and the effect of calpastatin on calpain activity under different phosphorylation levels was analyzed...

Calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) regulates bone remodeling through its effects on osteoblasts and osteoclasts. However, its role in osteocytes, the most abundant bone cell type and the master regulator of bone remodeling, remains unknown. Here we report that the conditional deletion of CaMKK2 from osteocytes using Dentine matrix protein 1 ( Dmp1 )-8kb- Cre mice led to enhanced bone mass only in female mice owing to a suppression of osteoclasts. Conditioned media isolated from female CaMKK2-deficient osteocytes inhibited osteoclast formation and function in in vitro assays, indicating a role for osteocyte-secreted factors...

Calpain and calpastatin are the key components of the calcium-dependent proteolytic system. Calpains are regulatory, calcium-dependent, cytoplasmic proteinases, and calpastatin is the endogenous inhibitor of calpains. Due to the correlation between changes in the activity of the calpain-calpastatin system in the brain and central nervous system (CNS) pathology states, this proteolytic system is a prime focus of research on CNS pathological processes, generally characterized by calpain activity upregulation...

Abnormal calcium homeostasis, activation of protease calpain, generation of p25 and hyperactivation of cyclin-dependent kinase 5 (Cdk5) have all been implicated in the pathogenesis of neurogenerative diseases including Alzheimer's disease. We have recently shown that extracellular cold-inducible RNA-binding protein (eCIRP) induces Cdk5 activation via p25. However, the precise molecular mechanism by which eCIRP regulates calcium signaling and calpain remains to be addressed. We hypothesized that eCIRP regulates p25 via Ca2+ -dependent calpain activation...