calpain and Wounds-and-Injuries

To review present knowledge of intracellular mechanisms and molecular regulation of muscle cachexia.. Muscle cachexia, mainly reflecting degradation of myofibrillar proteins, is an important clinical feature in patients with severe injury, sepsis, and cancer. The catabolic response in skeletal muscle may result in muscle wasting and weakness, delaying or preventing ambulation and rehabilitation in these patients and increasing the risk for pulmonary complications.. Muscle cachexia, induced by severe injury, sepsis, and cancer, is associated with increased gene expression and activity of the calcium/calpain- and ubiquitin/proteasome-proteolytic pathways. Calcium/calpain-regulated release of myofilaments from the sarcomere is an early, and perhaps rate-limiting, component of the catabolic response in muscle. Released myofilaments are ubiquitinated in the N-end rule pathway, regulated by the ubiquitin-conjugating enzyme E2(14k) and the ubiquitin ligase E3 alpha, and degraded by the 26S proteasome.. An understanding of the mechanisms regulating muscle protein breakdown is important for the development of therapeutic strategies aimed at treating or preventing muscle cachexia in patients with severe injury, sepsis, cancer, and perhaps other catabolic conditions as well.

Topics: Cachexia; Calcium; Calpain; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Multienzyme Complexes; Muscle, Skeletal; Neoplasms; Sepsis; Signal Transduction; Ubiquitins; Wounds and Injuries

Much recent research has focused on the pathological significance of calcium accumulation in the central nervous system (CNS) following cerebral ischemia, spinal cord injury (SCI), and traumatic brain injury (TBI). Disturbances in neuronal calcium homeostasis may result in the activation of several calcium-sensitive enzymes, including lipases, kinases, phosphatases, and proteases. One potential pathogenic event in a number of acute CNS insults, including TBI, is the activation of the calpains, calcium-activated intracellular proteases. This article reviews new evidence indicating that overactivation of calpains plays a major role in the neurodegenerative cascade following TBI in vivo. Further, this article presents an overview from in vivo and in vitro models of CNS injuries suggesting that administration of calpain inhibitors during the initial 24-h period following injury can attenuate injury-induced derangements of neuronal structure and function. Lastly, this review addresses the potential contribution of other proteases to neuronal damage following TBI.

Topics: Animals; Brain Injuries; Calpain; Endopeptidases; Wounds and Injuries

Calcium-activated nonlysosomal neutral proteases, calpains, are believed to be early mediators of neuronal damage associated with neuron death and axonal degeneration after traumatic neural injuries. In this study, a library of biologically active small molecular weight calpain inhibitors was used for model validation and inhibition site recognition. Subsequently, two natural neuroactive polyphenols, curcumin and quercetin, were tested for their sensitivity and activity towards calpain's proteolytic sequence and compared with the known calpain inhibitors via detailed molecular mechanics (MM), molecular dynamics (MD), and docking simulations. The MM and MD energy profiles (SJA6017 < AK275 < AK295 < PD151746 < quercetin < leupeptin < PD150606 < curcumin < ALLN < ALLM < MDL-28170 < calpeptin) and the docking analysis (AK275 < AK295 < PD151746 < ALLN < PD150606 < curcumin < leupeptin < quercetin < calpeptin < SJA6017 < MDL-28170 < ALLM) demonstrated that polyphenols conferred comparable calpain inhibition profiling. The modeling paradigm used in this study provides the first detailed account of corroboration of enzyme inhibition efficacy of calpain inhibitors and the respective calpain-calpain inhibitor molecular complexes' energetic landscape and in addition stimulates the polyphenol bioactive paradigm for post-SCI intervention with implications reaching to experimental in vitro, in cyto, and in vivo studies.

Topics: Amino Acid Sequence; Calpain; Computer Simulation; Cysteine Proteinase Inhibitors; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Sequence Data; Molecular Structure; Polyphenols; Wounds and Injuries

To investigate the expressions of calpain1 and calpain2 during the skin incised wound healing in mice.. Expression of calpain1 and calpain2 was evaluated by immunohistochemical method.. Both calpain1 and calpain2 were expressed in the skin cells in the control groups. The calpain1 positive cells were remarkably increased and reached the maximal level in day 1 after skin incised wound, decreased after day 3, markedly increased again in day 5, and then gradually decreased from day 7 to 14; the calpain2 positive cells were significantly increased in day 1 and decreased to the minimum in day 3, markedly increased again in day 5, and then gradually decreased from day 7 to 10.. The changes of calpain1 and calpain2 expressions appear to be bimodal after incised wound of skin in mice.

Topics: Animals; Apoptosis; Calpain; Disease Models, Animal; Female; Immunohistochemistry; Male; Mice; Random Allocation; Skin; Staining and Labeling; Time Factors; Wound Healing; Wounds and Injuries