A5088793975- Muscle Physiology and Disorders
- Adipose Tissue and Metabolism
- Muscle metabolism and nutrition
- Autophagy in Disease and Therapy
- Exercise and Physiological Responses
- Endoplasmic Reticulum Stress and Disease
- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- Sirtuins and Resveratrol in Medicine
- Animal Genetics and Reproduction
- Ubiquitin and proteasome pathways
- Cerebral Palsy and Movement Disorders
- Neutropenia and Cancer Infections
- Pharmacological Effects and Assays
- Lymphoma Diagnosis and Treatment
- Neurogenetic and Muscular Disorders Research
- Venomous Animal Envenomation and Studies
- Mesenchymal stem cell research
- Genetic Neurodegenerative Diseases
- Peripheral Neuropathies and Disorders
- Bacterial Identification and Susceptibility Testing
- Reproductive Physiology in Livestock
- Reproductive System and Pregnancy
- TGF-β signaling in diseases
- Hematological disorders and diagnostics
Centre for Research in Anthropology
2025
University of Lisbon
2025
Universidade de São Paulo
2008-2023
St. Jude Children's Research Hospital
2021-2023
Abstract Ubiquitination is a post-translational modification initiated by the E1 enzyme UBA1, which transfers ubiquitin to ~35 E2 ubiquitin-conjugating enzymes. While UBA1 loss cell lethal, it remains unknown how partial reduction in activity endured. Here, we utilize deep-coverage mass spectrometry define E1-E2 interactome and determine proteins that are modulated knockdown of each human cells. These analyses UBA1/E2-sensitive proteome specificity protein modulation. Interestingly, profound...
Abstract Skeletal muscle regeneration involves coordinated interactions between different cell types. Injection of platelet-rich plasma is circumstantially considered an aid to repair but whether platelets promote beyond their role in hemostasis remains unexplored. Here, we find that signaling via platelet-released chemokines early event necessary for mice. Platelet depletion reduces the levels platelet-secreted neutrophil chemoattractants CXCL5 and CXCL7/PPBP. Consequently, early-phase...
Although it is well known that administration of the selective β(2)-adrenergic agonist clenbuterol (CB) protects muscle following denervation (DEN), underlying molecular mechanism remains unclear. We report in vivo treatment with CB (3 mg/kg sc) for 3 days induces antiproteolytic effects normal and denervated rat soleus via distinct mechanisms. In muscle, stimulates protein synthesis, inhibits Ca(2+)-dependent proteolysis, increases levels calpastatin protein. On other hand, to DEN rats...
Abstract Aim To identify microRNAs (miRs) involved in the regulation of skeletal muscle mass. For that purpose, we have initially utilized an silico analysis, resulting identification miR‐29c as a positive regulator Methods was electrotransferred to tibialis anterior address its morphometric and functional properties determine level satellite cell proliferation differentiation. qPCR used investigate effect overexpression on trophicity‐related genes. C2C12 cells were impact myogenesis...
Skeletal muscle atrophy is a debilitating condition that occurs with aging and disease, but the underlying mechanisms are incompletely understood. Previous work determined common transcriptional changes occur in during induced by different stimuli. However, whether this holds true at proteome level remains largely unexplored. Here, we find that, contrary to earlier model, distinct atrophic stimuli (corticosteroids, cancer cachexia, aging) induce mRNA protein mice. Moreover, there widespread...
Abstract Background Stimulation of β 2 ‐adrenoceptors can promote muscle hypertrophy and fibre type shift, it counteract atrophy weakness. The underlying mechanisms remain elusive. Methods Fed wild (WT), 2‐day fasted WT, muscle‐specific insulin (INS) receptor (IR) knockout (M‐IR −/− ), MKR mice were studied with regard to acute effects the ‐agonist formoterol (FOR) on protein metabolism signalling events. express a dominant negative IGF1 receptor, which blocks both INS/IGF1 signalling. All...
Abstract Decline in skeletal muscle cell size (myofiber atrophy) is a key feature of cancer-induced wasting (cachexia). In particular, atrophy the diaphragm, major responsible for breathing, an important determinant cancer-associated mortality. However, therapeutic options are limited. Here, we have used Drosophila transgenic screening to identify muscle-secreted factors (myokines) that act as paracrine regulators myofiber growth. Subsequent testing mouse myotubes revealed Fibcd1...
Protein quality control is important for healthy aging and dysregulated in age-related diseases. The autophagy-lysosome ubiquitin-proteasome are key proteostasis, but it remains largely unknown whether other proteolytic systems also contribute to maintain proteostasis during aging. Here, we find that expression of enzymes (proteases/peptidases) distinct from the declines skeletal muscle Drosophila. Age-dependent protease downregulation undermines as demonstrated by increase...
Although we have recently demonstrated that plasma catecholamines induce antiproteolytic effects on skeletal muscle (Graça FA, Gonçalves DAP, Silveira WA, Lira EC, Chaves VE, Zanon NM, Garófalo MAR, Kettelhut IC, Navegantes LCC. Am J Physiol Endocrinol Metab. 305: E1483-E1494, 2013), the role of sympathetic innervation and, more specifically, norepinephrine (NE) in regulating ubiquitin (Ub)-proteasome system (UPS) remains unknown. Based previous findings chemical sympathectomy acutely...
Defects in protein quality control are the underlying cause of age-related diseases. The western blot analysis detergent-soluble and insoluble fractions has proven useful identifying interventions that regulate proteostasis. Here, we describe protocol for such analyses Drosophila tissues, mouse skeletal muscle, human organoids, HEK293 cells. We key adaptations this provide information will help modify future studies other tissues disease models. For complete details on use execution...
Myofiber atrophy occurs with aging and in many diseases but the underlying mechanisms are incompletely understood. Here, we have used >1,100 muscle-targeted RNAi interventions to comprehensively assess function of 447 transcription factors developmental growth body wall skeletal muscles Drosophila. This screen identifies new regulators myofiber hypertrophy, including factor Deaf1. Deaf1 increases size whereas overexpression induces atrophy. Consistent its annotation as a Gsk3 phosphorylation...
Abstract Platelets have important hemostatic functions in repairing blood vessels upon tissue injury. Cytokines, growth factors, and metabolites stored platelet α‐granules dense granules are released activation clotting. Emerging evidence indicates that such platelet‐derived signaling factors instrumental guiding regeneration. Here, we discuss the roles of platelet‐secreted skeletal muscle Chemokines secreted by platelets early phase after injury needed to recruit neutrophils injured...
The physiological role of epinephrine in the regulation skeletal muscle protein metabolism under fasting is unknown. We examined effects plasma depletion, induced by adrenodemedullation (ADMX), on fed and 2-day-fasted rats. In rats, ADMX for 10 days reduced mass, cross-sectional area extensor digitorum longus (EDL) fibers, phosphorylation levels Akt. addition, led to a compensatory increase sympathetic activity, as estimated rate norepinephrine turnover; this was accompanied high rates...
Cachexia is a systemic wasting syndrome that increases cancer-associated mortality. How cachexia progressively and differentially impacts distinct tissues largely unknown. Here, we find the heart skeletal muscle undergo at early stages are transcriptionally most impacted by cachexia. We also identify general organ-specific transcriptional changes indicate functional derangement even in do not wasting, such as brain. Secreted factors constitute top category of cancer-regulated genes host...
Historically, qualitative research has complemented quantitative biologic and epidemiologic studies to provide a more complete understanding of pandemics. The COVID-19 pandemic generated unique novel challenges for researchers, who have embraced creative solutions including virtual focus groups rapid analyses continue their work. We present our experience conducting multilingual global study healthcare resilience among teams pediatric oncology professionals during the pandemic. an in-depth...
Muscle loss occurs following injury and immobilization in adulthood childhood, which impairs the rehabilitation process; however, far fewer studies have been conducted analyzing atrophic response infants. This work investigated first morphological molecular mechanisms involved immobilization-induced atrophy soleus muscles from rats at different stages of postnatal development [i.e., weanling (WR) adult (AR) rats] and, second, role autophagy regulating muscle plasticity during immobilization....
This study investigated the in vivo effects of Bothrops jararaca venom (BjV) on general metabolic profile and, specifically, muscle protein metabolism rats. The crude (0.4 mg/kg body weight, IV) was infused awake rats, and plasma activity enzymes metabolites levels were determined after 1, 2, 3, 4 hours. BjV increased urea, lactate, activities creatine kinase, lactate dehydrogenase, aspartate aminotransferase content liver glycogen reduced by BjV. Protein evaluated means microdialysis...
Although there are reports that polyphenol resveratrol (Rsv) may cause muscle hypertrophy in basal conditions and attenuate wasting catabolic situations, its mechanism of action is still unclear. Our study evaluated the ex vivo effects Rsv on protein metabolism intracellular signaling innervated (sham-operated; Sham) 3-day sciatic denervated (Den) rat skeletal muscles. (10-4 M) reduced total proteolysis (40%) sham Den increased (~40%) muscle, which was accompanied by an increase activities...
Aging and wasting of skeletal muscle reduce organismal fitness. Regrettably, only limited interventions are currently available to address this unmet medical need. Many methods have been developed study condition, including the intramuscular electroporation DNA plasmids. However, technique requires surgery high electrical fields, which cause tissue damage. Here, we report an optimized protocol for small interfering RNAs (siRNAs) into tibialis anterior mice. This does not require and, because...
This study was undertaken to identify: 1) whether ß 2 ‐adrenergic agonist (BA) suppresses Foxo transcriptional activity and the expression of atrophy‐related genes (atrogenes) in skeletal muscles 2) which post‐translational modification [ i.e., phosphorylation (p) acetylation (ac)] is related inhibition Foxo1. For that, we examined Formoterol (FOR), a newer generation BA, effects on levels p‐Foxo1, ac‐Foxo1, p‐Akt p‐CREB, canonical target BA signaling, by immunoblotting, reporter luciferase...
The present work investigated the physiological role of epinephrine in control muscle protein degradation during fasting. For this, 3‐week‐old rats, previously submitted to adrenodemedullation (ADMX; 10 d after surgical removal adrenal medulla) were fasted for 2 days. ADMX abolished plasma concentration both fed and animals but did not affect corticosterone levels. In sham fasting increased overall proteolysis, activity ubiquitin‐proteasome system (UPS), mRNA levels atrogenes (Atrogin‐1...