Calpains are intracellular nonlysosomal Ca(2+-) regulated cysteine proteases, widely located in the tissues of most mammals. Skeletal muscle tissue mainly expresses m-calpain, µ-caplain, n-calpain, and their endogenous inhibitor calpastatin. They are closely related to the cell apoptosis, cytoskeleton formation, cell cycles, etc. Calpains are also considered to be participating in the protein degradation process. Severe burns are typically followed by hypermetabolic responses that are characterized by hyperdynamic circulatory responses with increased proteolysis and cell apoptosis. Recently, overloading of Ca(2+) in skeletal muscle cells, which activates the calpains is observed after a serious burn. This paper aims to review the current research of the relationship between calpains and post-burn skeletal muscle wasting from the perspectives of structure, function, and physiological activities.
Animals ; Burns ; metabolism ; pathology ; Calpain ; metabolism ; Muscle, Skeletal ; metabolism ; pathology

Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs, which is mediated by cancer cachexia factors. Cancer cachexia factors, being the general name of inflammatory factors, circulating proteins, metabolites, and microRNA secreted by tumor or host cells, play a role in secretory or other organs and mediate complex signal communication between organs during cancer cachexia. Cancer cachexia factors are also a potential target for the diagnosis and treatment. The pathogenesis of cachexia is unclear and no clear effective treatment is available. Thus, the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently needed. From the point of signal communication between organs mediated by cancer cachexia factors, finding a deeper understanding of the pathogenesis, diagnosis, and treatment of cancer cachexia is of great significance to improve the level of diagnosis and treatment. This review begins with cancer cachexia factors released during the interaction between tumor and host cells, and provides a comprehensive summary of the pathogenesis, diagnosis, and treatment for cancer cachexia, along with a particular sight on multi-organ signal communication mediated by cancer cachexia factors. This summary aims to deepen medical community's understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.
Humans ; Cachexia/pathology* ; Ecosystem ; Neoplasms/metabolism* ; Syndrome ; Muscle, Skeletal/pathology*

Most of the major advances in burn treatment were made within the last five decades. However, hypermetabolic response after severe burn remains a problem in the treatment of patients with massive burn. As skeletal muscle accounts for over 50% of body cell dry weight, its catabolism exerts profound effect on body metabolism as a whole. Main mechanisms underlying skeletal muscle wasting induced by severe burn include activation of ubiquitin-proteasome pathway, bringing about breakdown of muscle protein, and myonuclear apoptosis. Therapeutic strategies for skeletal muscle wasting after burn mainly include maintenance of room temperature at (31.5 +/- 0.7) degrees C, early active and passive exercise of skeletal muscles, administration of beta adrenergic receptor blocker such as Propranolol, recombinant growth hormone, androgen, and insulin, which has lately been proven to possess the effect of suppressing myonuclear apoptosis after burn. Combination of multiple therapeutic strategies is beneficial in reducing complications of burn patients, particularly wide ranged skeletal muscle atrophy, to achieve a better clinical outcome.
Apoptosis ; Burns ; drug therapy ; metabolism ; pathology ; Humans ; Muscle, Skeletal ; metabolism

Angiotensin II ; metabolism ; Animals ; Male ; Muscle, Skeletal ; Muscular Atrophy ; etiology ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley

Actins ; metabolism ; Adult ; Desmin ; metabolism ; Electromyography ; Humans ; Male ; Microscopy, Electron, Transmission ; Muscle, Skeletal ; pathology ; ultrastructure ; Myopathies, Nemaline ; metabolism ; pathology

RING finger protein 13 (RNF13) is a newly identified E3 ligase reported to be functionally significant in the regulation of cancer development, muscle cell growth, and neuronal development. In this study, the function of RNF13 in cardiotoxin-induced skeletal muscle regeneration was investigated using RNF13-knockout mice. RNF13(-/-) mice exhibited enhanced muscle regeneration-characterized by accelerated satellite cell proliferation-compared with wild-type mice. The expression of RNF13 was remarkably induced in macrophages rather than in the satellite cells of wild-type mice at the very early stage of muscle damage. This result indicated that inflammatory cells are important in RNF13-mediated satellite cell functions. The cytokine levels in skeletal muscles were further analyzed and showed that RNF13(-/-) mice produced greater amounts of various cytokines than wild-type mice. Among these, IL-4 and IL-6 levels significantly increased in RNF13(-/-) mice. The accelerated muscle regeneration phenotype was abrogated by inhibiting IL-4/IL-6 action in RNF13(-/-) mice with blocking antibodies. These results indicate that RNF13 deficiency promotes skeletal muscle regeneration via the effects on satellite cell niche mediated by IL-4 and IL-6.
Animals ; Cell Proliferation ; Inflammation ; pathology ; Interleukin-4 ; metabolism ; Interleukin-6 ; metabolism ; Macrophages ; metabolism ; Mice ; Mice, Knockout ; Muscle, Skeletal ; metabolism ; pathology ; physiopathology ; Regeneration ; Satellite Cells, Skeletal Muscle ; metabolism ; pathology ; Ubiquitin-Protein Ligases ; deficiency ; metabolism

OBJECTIVETo identify potential mutations in patients featuring Becker muscular dystrophy (BMD) and to enhance the understanding of non-deletion/duplication mutations of the dystrophin gene causing BMD.

METHODSClinical data of two patients affected with BMD were collected. Potential mutations in the dystrophin gene were screened with multiplex ligation-dependent probe amplification assay (MLPA). Biopsied muscle samples were examined with HE staining, immnostaining with anti-dystrophin antibody, and electronic microscopy.

RESULTSMLPA assay suggested that both cases were probably due to non-deletion/duplication mutations of the dystrophin gene. Light and electronic microcopy of skeletal muscle biopsies confirmed dystrophic changes in both patients. For patient A, immunostaining showed non-contiguous weak staining for most parts of sarcolemma. For patient B, immunostaining showed positive result with N-terminal anti-dystrophin antibody and negative result with C-terminal anti-dystrophin antibody.

CONCLUSIONFor patients with mild phenotypes but without dystrophin gene deletion/duplication, muscle biopsy and immunochemistry are helpful for diagnosis and prognosis.

Adolescent ; Adult ; Dystrophin ; genetics ; metabolism ; Humans ; Male ; Muscle, Skeletal ; pathology ; Muscular Dystrophy, Duchenne ; genetics ; metabolism ; pathology ; Mutation ; genetics

PURPOSE: The purpose of this study was to examine the effect of anorexia and neuropathic pain induced by cisplatin on hindlimb muscles of rats. METHODS: Adult male Sprague-Dawley rats were divided into two groups, a cisplatin-treated group (n=10) and a control group (n=10). In the cisplatin-treated group, cisplatin at a dose of 2 mg/kg was injected intraperitoneally two times a week up to a cumulative dose of 20 mg/kg over 5 weeks, and in the control group saline (0.9% NaCl) was injected intraperitoneally at the same dose and duration as the cisplatin-treated group. At 34 days all rats were anesthetized, after which the soleus and plantaris muscles were dissected. Withdrawal threshold, body weight, food intake, activity, muscle weight, Type I and II fiber cross-sectional areas and myofibrillar protein content of the dissected muscles were determined. RESULTS: Compared with the control group, the cisplatin-treated group showed significant decreases (p<.05) in withdrawal threshold, activity, food intake, body weight, Type I and II fiber cross-sectional areas, myofibrillar protein content and weight of the soleus and plantaris muscles. CONCLUSION: Muscular atrophy in hindlimb occurs due to anorexia and neuropathic pain induced by the cisplatin treatment.
Animals ; *Anorexia ; Body Weight ; Cisplatin/*toxicity ; Eating ; Hindlimb ; Injections, Intraperitoneal ; Male ; Motor Activity ; Muscle Fibers, Skeletal/metabolism/pathology ; Muscle Proteins/metabolism ; Muscle, Skeletal/*drug effects/physiology ; Neuralgia/*chemically induced/pathology ; Rats ; Rats, Sprague-Dawley

Diabetes mellitus is a complex metabolic disorder characterized by chronic hyperglycemia due to absolute or relative lack of insulin. Though great efforts have been made to investigate the pathogenesis of diabetes, the underlying mechanism behind the development of diabetes and its complications remains unexplored. Cumulative evidence has linked mitochondrial modification to the pathogenesis of diabetes and its complications and they are also observed in various tissues affected by diabetes. Proteomics is an attractive tool for the study of diabetes since it allows researchers to compare normal and diabetic samples by identifying and quantifying the differentially expressed proteins in tissues, cells or organelles. Great progress has already been made in mitochondrial proteomics to elucidate the role of mitochondria in the pathogenesis of diabetes and its complications. Further studies on the changes of mitochondrial protein specifically post-translational modifications during the diabetic state using proteomic tools, would provide more information to better understand diabetes.
Adipose Tissue ; metabolism ; Diabetes Complications ; Diabetes Mellitus ; metabolism ; pathology ; Humans ; Insulin ; metabolism ; Insulin-Secreting Cells ; cytology ; metabolism ; Liver ; metabolism ; Mitochondria ; metabolism ; Muscle, Skeletal ; metabolism ; Proteome ; metabolism ; Proteomics

BACKGROUNDTherapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue perfusion. Nerve growth factor (NGF) has been reported to play an important role in both physiological and pathological angiogenesis. This study aimed to investigate the effects of NGF on angiogenesis and skeletal muscle fiber remodeling in a murine model of hindlimb ischemia and study the relationship between NGF and vascular endothelial growth factor (VEGF) in angiogenesis.

METHODSTwenty-four mice were randomly allocated to normal control group (n = 6), blank control group (n = 6), VEGF gene transfection group (n = 6), and NGF gene transfection group (n = 6). The model of left hindlimb ischemia model was established by ligating the femoral artery. VEGF165plasmid (125 μg) and NGF plasmid (125 μg) was injected into the ischemic gastrocnemius of mice from VEGF group and NGF group, respectively. Left hindlimb function and ischemic damage were assessed with terminal points at 21th day postischemia induction. The gastrocnemius of four groups was tested by hematoxylin-eosin staining, proliferating cell nuclear antigen and CD34 immunohistochemistry staining, and myosin ATPase staining. NGF and VEGF protein expression was detected by enzyme-linked immunosorbent assay.

RESULTSOn the 21th day after surgery, the functional assessment score and skeletal muscle atrophy degree of VEGF group and NGF group were significantly lower than those of normal control group and blank control group. The endothelial cell proliferation index and the capillary density of VEGF group and NGF group were significantly increased compared with normal control group and blank control group (P < 0.05). The NGF and VEGF protein expression of NGF group showed a significant rise when compared with blank control group (P < 0.05). Similarly, the VEGF protein expression of VEGF group was significantly higher than that of blank control group (P < 0.05), but there was no significant difference of the NGF protein expression between VEGF group and blank control group (P > 0.05). The type I skeletal muscle fiber proportion in gastrocnemius of NGF group and VEGF group was significantly higher than that of blank control group (P < 0.05).

CONCLUSIONSNGF transfection can promote NGF and VEGF protein expression which not only can induce angiogenesis but also induce type I muscle fiber expression in ischemic limbs.

Animals ; Antigens, CD34 ; metabolism ; Female ; Hindlimb ; metabolism ; pathology ; Ischemia ; metabolism ; pathology ; Mice ; Muscle, Skeletal ; metabolism ; pathology ; Neovascularization, Physiologic ; genetics ; physiology ; Random Allocation ; Vascular Endothelial Growth Factor A ; genetics ; physiology