RESUMEN
Ischemia and reperfusion events, such as myocardial infarction (MI), are reported to induce remote organ damage severely compromising patient outcomes. Tissue survival and functional restoration relies on the activation of endogenous redox regulatory systems such as the oxidoreductases of the thioredoxin (Trx) family. Trxs and peroxiredoxins (Prxs) are essential for the redox regulation of protein thiol groups and for the reduction of hydrogen peroxide, respectively. Here, we determined whether experimental MI induces changes in Trxs and Prxs in the heart as well as in secondary organs. Levels and localization of Trx1, TrxR1, Trx2, Prx1, and Prx2 were analyzed in the femur, vertebrae, and kidneys of rats following MI or sham surgery. Trx1 levels were significantly increased in the heart (P = 0.0017) and femur (P < 0.0001) of MI animals. In the femur and lumbar vertebrae, Trx1 upregulation was detected in bone-lining cells, osteoblasts, megakaryocytes, and other hematopoietic cells. Serum levels of Trx1 increased significantly 2 days after MI compared to sham animals (P = 0.0085). Differential regulation of Trx1 in the bone was also detected by immunohistochemistry 1 month after MI. N-Acetyl-cysteine treatment over a period of 1 month induced a significant reduction of Trx1 levels in the bone of MI rats compared to sham and to MI vehicle. This study provides first evidence that MI induces remote organ upregulation of the redox protein Trx1 in the bone, as a response to ischemia-reperfusion injury in the heart.
Asunto(s)
Médula Ósea/metabolismo , Huesos/metabolismo , Infarto del Miocardio/metabolismo , Tiorredoxinas/metabolismo , Regulación hacia Arriba , Animales , Médula Ósea/patología , Huesos/patología , Masculino , Infarto del Miocardio/patología , Ratas , Ratas Endogámicas F344 , Tiorredoxinas/análisisRESUMEN
Extensive research has changed the understanding of oxidative stress that has been linked to every major disease. Today we distinguish oxidative eu- and distress, acknowledging that redox modifications are crucial for signal transduction in the form of specific thiol switches. Long underestimated, reactive species and redox proteins of the Thioredoxin (Trx) family are indeed essential for physiological processes. Moreover, extracellular redox proteins, low molecular weight thiols and thiol switches affect signal transduction and cell-cell communication. Here, we highlight the impact of extracellular redox regulation for health, intermediate pathophenotypes and disease. Of note, recent advances allow the analysis of redox changes in body fluids without using invasive and expensive techniques. With this new knowledge in redox biochemistry, translational strategies can lead to innovative new preventive and diagnostic tools and treatments in life sciences and medicine.
RESUMEN
The proteins from the thioredoxin family are crucial actors in redox signaling and the cellular response to oxidative stress. The major intracellular source for oxygen radicals are the components of the respiratory chain in mitochondria. Here, we show that the mitochondrial 2-Cys peroxiredoxin (Prx3) is not only substrate for thioredoxin 2 (Trx2), but can also be reduced by glutaredoxin 2 (Grx2) via the dithiol reaction mechanism. Grx2 reduces Prx3 exhibiting catalytic constants (K(m), 23.8 µmol·liter(-1); V(max), 1.2 µmol·(mg·min)(-1)) similar to Trx2 (K(m), 11.2 µmol·liter(-1); V(max), 1.1 µmol·(mg·min)(-1)). The reduction of the catalytic disulfide of the atypical 2-Cys Prx5 is limited to the Trx system. Silencing the expression of either Trx2 or Grx2 in HeLa cells using specific siRNAs did not change the monomer:dimer ratio of Prx3 detected by a specific 2-Cys Prx redox blot. Only combined silencing of the expression of both proteins led to an accumulation of oxidized protein. We further demonstrate that the distribution of Prx3 in different mouse tissues is either linked to the distribution of Trx2 or Grx2. These results introduce Grx2 as a novel electron donor for Prx3, providing further insights into pivotal cellular redox signaling mechanisms.
Asunto(s)
Glutarredoxinas/metabolismo , Mitocondrias/enzimología , Proteínas Mitocondriales/metabolismo , Peroxirredoxinas/metabolismo , Tiorredoxinas/metabolismo , Animales , Femenino , Regulación del Desarrollo de la Expresión Génica/fisiología , Silenciador del Gen , Glutarredoxinas/genética , Células HeLa , Humanos , Ratones , Mitocondrias/genética , Proteínas Mitocondriales/genética , Especificidad de Órganos/fisiología , Oxidación-Reducción , Estrés Oxidativo/fisiología , Peroxiredoxina III , Peroxirredoxinas/genética , Multimerización de Proteína/fisiología , Ratas , Tiorredoxinas/genéticaRESUMEN
Ischemia-reperfusion injury (IRI) is the leading cause of acute renal failure and is a significant contributor to delayed graft function. Animal models are the only available resources that mimic the complexities of the IRI-associated damage encountered in vivo. This paper describes an effective mouse model of unilateral renal IRI that delivers highly reproducible data. Ischemia is induced by occluding the right renal pedicle for 30 min followed by reperfusion. In addition to the surgical procedure, a sequential overview of the expected physiological and histopathological changes following renal IRI will be provided by comparing data from seven different reperfusion times (4 h, 8 h, 16 h, 1 day, 2 days, 4 days, and 7 days). Critical data for planning experiments ahead, such as mean surgical time, average anesthetic consumption, and body weight changes over time, will be shared. This work will help researchers implement a reliable renal IRI model and select the appropriate reperfusion time that aligns with their intended investigative goals.
Asunto(s)
Lesión Renal Aguda , Daño por Reperfusión , Lesión Renal Aguda/etiología , Animales , Modelos Animales de Enfermedad , Isquemia , Riñón , RatonesRESUMEN
Mammalian glutaredoxin 3 (Grx3/PICOT) is an essential protein involved in the regulation of signal transduction, for instance during immune cell activation and development of cardiac hypertrophy, presumably in response to redox signals. This function requires the sensing of such stresses by a hitherto unknown mechanism. Here, we characterized Grx3/PICOT as iron-sulfur protein. The protein binds two bridging [2Fe-2S] clusters in a homodimeric complex with the active site cysteinyl residues of its two monothiol glutaredoxin domains and glutathione bound non-covalently to the Grx domains. Co-immunoprecipitation of 55-iron with Grx3/PICOT from Jurkat cells suggested the presence of these cofactors under physiological conditions. The [2Fe-2S]2+ clusters were not redox active, instead they were lost upon treatment of the holo protein with ferricyanide or S-nitroso glutathione. This redox-induced dissociation of the Grx3/PICOT holo complex may be a mechanism of Grx3/PICOT activation in response to reactive oxygen and nitrogen species.
Asunto(s)
Proteínas Portadoras/metabolismo , Proteínas Hierro-Azufre/metabolismo , Hierro/metabolismo , Proteínas Portadoras/química , Ferricianuros/metabolismo , Humanos , Inmunoprecipitación , Radioisótopos de Hierro/metabolismo , Proteínas Hierro-Azufre/química , Células Jurkat , Oxidación-Reducción , Conformación Proteica , Estabilidad Proteica , Estructura Terciaria de Proteína , S-Nitrosoglutatión/metabolismoRESUMEN
Nucleoredoxin (Nrx) is an oxidoreductase of the thioredoxin family of proteins. It was shown to act as a signal transducer in some pathways; however, so far, no comprehensive analysis of its regulated substrates and functions was available. Here, we used a combination of two different strategies to fill this gap. First, we analyzed the thiol-redox state of the proteome of SH-SY5Y neuroblastoma cells depleted of Nrx compared to control cells using a differential thiol-labeling technique and quantitative mass spectrometry. 171 proteins were identified with an altered redox state; 161 of these were more reduced in the absence of Nrx. This suggests functions of Nrx in the oxidation of protein thiols. Second, we utilized the active site mutant Cys208Ser of Nrx, which stabilizes a mixed disulfide intermediate with its substrates and therefore trapped interacting proteins from the mouse brain (identifying 1710 proteins) and neuronal cell culture extracts (identifying 609 proteins). Profiling of the affected biological processes and molecular functions in cells of neuronal origin suggests numerous functions of Nrx in the redox regulation of metabolic pathways, cellular morphology, and signal transduction. These results characterize Nrx as a cellular oxidase that itself may be oxidized by the formation of disulfide relays with peroxiredoxins.
Asunto(s)
Neuronas/metabolismo , Proteínas Nucleares/metabolismo , Oxidorreductasas/metabolismo , Animales , Western Blotting , Encéfalo/metabolismo , Línea Celular Tumoral , Electroforesis en Gel de Poliacrilamida , Humanos , Ratones , Proteínas Nucleares/genética , Oxidación-Reducción , Oxidorreductasas/genéticaRESUMEN
The 'Solute Carrier Family SLC10' consists of six annotated members in humans, comprising two bile acid carriers (SLC10A1 and SLC10A2), one steroid sulfate transporter (SLC10A6), and three orphan carriers (SLC10A3 to SLC10A5). In this study we report molecular characterization and expression analysis of a novel member of the SLC10 family, SLC10A7, previously known as C4orf13. SLC10A7 proteins consist of 340-343 amino acids in humans, mice, rats, and frogs and show an overall amino acid sequence identity of >85%. SLC10A7 genes comprise 12 coding exons and show broad tissue expression pattern. When expressed in Xenopus laevis oocytes and HEK293 cells, SLC10A7 was detected in the plasma membrane but revealed no transport activity for bile acids and steroid sulfates. By immunofluorescence analysis of dual hemagglutinin (HA)- and FLAG-labeled SLC10A7 proteins in HEK293 cells, we established a topology of 10 transmembrane domains with an intracellular cis orientation of the N-terminal and C-terminal ends. This topology pattern is clearly different from the seven-transmembrane domain topology of the other SLC10 members but similar to hitherto uncharacterized non-vertebrate SLC10A7-related proteins. In contrast to the established SLC10 members, which are restricted to the taxonomic branch of vertebrates, SLC10A7-related proteins exist also in yeasts, plants, and bacteria, making SLC10A7 taxonomically the most widespread member of this carrier family. Vertebrate and bacterial SLC10A7 proteins exhibit >20% sequence identity, which is higher than the sequence identity of SLC10A7 to any other member of the SLC10 carrier family.
Asunto(s)
Bacterias/genética , Secuencia Conservada , Transportadores de Anión Orgánico Sodio-Dependiente/genética , Filogenia , Vertebrados/genética , Empalme Alternativo/genética , Secuencia de Aminoácidos , Animales , Transporte Biológico , Membrana Celular/metabolismo , Clonación Molecular , Exones/genética , Genoma , Humanos , Inmunoprecipitación , Ratones , Datos de Secuencia Molecular , Oocitos , Transportadores de Anión Orgánico Sodio-Dependiente/química , Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Ratas , Proteínas Recombinantes de Fusión/metabolismo , Simportadores/metabolismo , XenopusRESUMEN
It is currently controversially discussed whether mesenchymal stem cells (MSC) facilitate cartilage regeneration in vivo by a progenitor- or a nonprogenitor-mediated mechanism. Here, we describe a potentially novel unbiased in vivo cell tracking system based on transgenic donor and corresponding immunocompetent marker-tolerant recipient mouse and rat lines in inbred genetic backgrounds. Tolerance of recipients was achieved by transgenic expression of an immunologically neutral but physicochemically distinguishable variant of the marker human placental alkaline phosphatase (ALPP). In this dual transgenic system, donor lines ubiquitously express WT, heat-resistant ALPP protein, whereas recipient lines express a heat-labile ALPP mutant (ALPPE451G) resulting from a single amino acid substitution. Tolerance of recipient lines to ALPP-expressing cells and tissues was verified by skin transplantation. Using this model, we show that intraarticularly injected MSC contribute to regeneration of articular cartilage in full-thickness cartilage defects mainly via a nonprogenitor-mediated mechanism.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/inmunología , Regeneración/inmunología , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Animales , Cartílago Articular/citología , Diferenciación Celular , Células Cultivadas , Modelos Animales de Enfermedad , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Humanos , Inyecciones Intraarticulares , Trasplante de Islotes Pancreáticos , Isoenzimas/genética , Isoenzimas/metabolismo , Masculino , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/fisiología , Ratones , Ratones Transgénicos , Ratas , Ratas Transgénicas , Trasplante de PielRESUMEN
Monothiol glutaredoxins (Grxs) with a noncanonical CGFS active site are found in all kingdoms of life. They include members with a single domain and thioredoxin-Grx fusion proteins. In Saccharomyces cerevisiae, the multidomain Grx3 and Grx4 play an essential role in intracellular iron trafficking. This crucial task is mediated by an essential Fe/S cofactor. This study shows that this unique physiological role cannot be executed by single domain Grxs, because the thioredoxin domain is indispensable for function in vivo. Mutational analysis revealed that a CPxS active site motif is fully compatible with Fe/S cluster binding on Grx4, while a dithiol active site results in cofactor destabilization and a moderate impairment of in vivo function. These requirements for Fe/S cofactor stabilization on Grx4 are virtually the opposite of those previously reported for single domain Grxs. Grx4 functions as iron sensor for the iron-sensing transcription factor Aft1 in S. cerevisiae. We found that Aft1 binds to a conserved binding site at the C-terminus of Grx4. This interaction is essential for the regulation of Aft1. Collectively, our analysis demonstrates that the multidomain monothiol Grxs form a unique protein family distinct from that of the single domain Grxs.
Asunto(s)
Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Dominio Catalítico , Glutarredoxinas/genética , Glutarredoxinas/metabolismo , Estructura Terciaria de Proteína , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Tiorredoxinas/genética , Tiorredoxinas/metabolismoRESUMEN
The disruption of redox control, i.e., oxidative stress, is one of the most destructive causes of ischemia-reperfusion (IR) injury. Thioredoxin (Trx) family proteins play a major role in the cellular response to oxidative stress. Here, we systematically investigated the levels and tissue distribution of 15 members of this family (Trx and TrxR 1 and 2, Nrx, Prx 1-6, and Grx 1-3 and 5) in mouse kidneys after induction of IR by comparing control, clamped, and contralateral organs. After IR, levels of various redoxins were quantified. Immunohistochemical analysis revealed segment-specific alterations induced by the ischemic insult. Grx2, Prx3, and Prx6 were highly expressed in proximal tubule cells. Overexpression of these proteins in HEK293 and HeLa cells subjected to hypoxia and reoxygenation revealed higher survival and proliferation rates and lower oxidative damage compared to controls. Furthermore, we report for the first time the accumulation of Grx1 at the apical side of distal convoluted cells and the specific secretion of Grx1 into the urine after IR. The differences in both the basal equipment and the segment-specific responses of the antioxidant proteins may contribute to the distinct susceptibilities and regeneration processes of the various segments of the nephron to the IR insult.
Asunto(s)
Glutarredoxinas/fisiología , Riñón/irrigación sanguínea , Peroxiredoxina VI/fisiología , Peroxirredoxinas/fisiología , Daño por Reperfusión/prevención & control , Animales , Secuencia de Bases , Western Blotting , Cartilla de ADN , Masculino , Ratones , Ratones Endogámicos C57BL , Daño por Reperfusión/enzimologíaRESUMEN
Iron is an essential nutrient for cells. It is unknown how iron, after its import into the cytosol, is specifically delivered to iron-dependent processes in various cellular compartments. Here, we identify an essential function of the conserved cytosolic monothiol glutaredoxins Grx3 and Grx4 in intracellular iron trafficking and sensing. Depletion of Grx3/4 specifically impaired all iron-requiring reactions in the cytosol, mitochondria, and nucleus, including the synthesis of Fe/S clusters, heme, and di-iron centers. These defects were caused by impairment of iron insertion into proteins and iron transfer to mitochondria, indicating that intracellular iron is not bioavailable, despite highly elevated cytosolic levels. The crucial task of Grx3/4 is mediated by a bridging, glutathione-containing Fe/S center that functions both as an iron sensor and in intracellular iron delivery. Collectively, our study uncovers an important role of monothiol glutaredoxins in cellular iron metabolism, with a surprising connection to cellular redox and sulfur metabolisms.
Asunto(s)
Citosol/metabolismo , Glutarredoxinas/metabolismo , Hierro/metabolismo , Transporte Biológico , Proteínas Hierro-Azufre , Oxidación-Reducción , Oxidorreductasas/metabolismo , Proteínas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Azufre/metabolismo , Levaduras/metabolismoRESUMEN
Here we report the identification, cloning, and characterization of SLC10A5, which is a new member of Solute Carrier Family 10 (SLC10), also known as the "sodium/bile acid cotransporter family". Expression of SLC10A5/Slc10a5 was examined by quantitative real-time PCR and revealed its highest expression levels in liver and kidney in humans, rat and mouse. In rat liver and kidney, Slc10a5 expression was localized by in situ hybridization to hepatocytes and proximal tubules, respectively. A SLC10A5-FLAG fusion protein was expressed in HEK293 cells and showed an apparent molecular weight of 42 kDa after immunoprecipitation. When expressed in Xenopus laevis oocytes, the SLC10A5-FLAG protein was detected in the oocyte's plasma membrane but showed no transport activity for taurocholate, cholate, estrone-3-sulfate, or dehydroepiandrosterone sulfate. As bile acid carriers are the most related carriers to SLC10A5 though, we strongly suppose that SLC10A5 is an orphan carrier with yet non-identified substrates.
Asunto(s)
Riñón/metabolismo , Hígado/metabolismo , Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Simportadores/metabolismo , Secuencia de Aminoácidos , Animales , Clonación Molecular , Expresión Génica , Humanos , Ratones , Datos de Secuencia Molecular , Oocitos/metabolismo , Transportadores de Anión Orgánico Sodio-Dependiente/química , Transportadores de Anión Orgánico Sodio-Dependiente/genética , Ratas , Simportadores/química , Simportadores/genética , Xenopus laevisRESUMEN
We have cloned human sodium-dependent organic anion transporter (SOAT) cDNA, which consists of 1502 bp and encodes a 377-amino acid protein. SOAT shows 42% sequence identity to the ileal apical sodium-dependent bile acid transporter ASBT and 33% sequence identity to the hepatic Na(+)/taurocholate-cotransporting polypeptide NTCP. Immunoprecipitation of a SOAT-FLAG-tagged protein revealed a glycosylated form at 46 kDa that decreased to 42 kDa after PNGase F treatment. SOAT exhibits a seven-transmembrane domain topology with an outside-to-inside orientation of the N-terminal and C-terminal ends. SOAT mRNA is most highly expressed in testis. Relatively high SOAT expression was also detected in placenta and pancreas. We established a stable SOAT-HEK293 cell line that showed sodium-dependent transport of dehydroepiandrosterone sulfate, estrone-3-sulfate, and pregnenolone sulfate with apparent K(m) values of 28.7, 12.0, and 11.3 microm, respectively. Although bile acids, such as taurocholic acid, cholic acid, and chenodeoxycholic acid, were not substrates of SOAT, the sulfoconjugated bile acid taurolithocholic acid-3-sulfate was transported by SOAT-HEK293 cells in a sodium-dependent manner and showed competitive inhibition of SOAT transport with an apparent K(i) value of 0.24 mum. Several nonsteroidal organosulfates also strongly inhibited SOAT, including 1-(omega-sulfooxyethyl)pyrene, bromosulfophthalein, 2- and 4-sulfooxymethylpyrene, and alpha-naphthylsulfate. Among these inhibitors, 2- and 4-sulfooxymethylpyrene were competitive inhibitors of SOAT, with apparent K(i) values of 4.3 and 5.5 microm, respectively, and they were also transported by SOAT-HEK293 cells.
Asunto(s)
Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Transportadores de Anión Orgánico/metabolismo , Procesamiento Proteico-Postraduccional/fisiología , Secuencia de Aminoácidos , Transporte Biológico Activo/efectos de los fármacos , Transporte Biológico Activo/fisiología , Línea Celular , Clonación Molecular , ADN Complementario/genética , ADN Complementario/metabolismo , Femenino , Humanos , Masculino , Moduladores del Transporte de Membrana/farmacología , Datos de Secuencia Molecular , Especificidad de Órganos/fisiología , Transportadores de Anión Orgánico/genética , Transportadores de Anión Orgánico Sodio-Dependiente/genética , Páncreas/metabolismo , Placenta/metabolismo , Embarazo , Homología de Secuencia de Aminoácido , Simportadores/genética , Testículo/metabolismoRESUMEN
In this study, a novel sodium-dependent organic anion transporter (Soat) was identified. Soat is expressed in rat brain, heart, kidney, lung, muscle, spleen, testis, adrenal gland, small intestine, and colon. The Soat protein consists of 370 amino acids and shows 42% and 31% overall amino acid sequence identity to the ileal sodium-dependent bile acid transporter (Isbt) and the Na(+)/taurocholate cotransporting polypeptide (Ntcp), respectively. Soat is predicted to have nine transmembrane domains, with an N-terminus outside the cell and an intracellular C-terminus. The Soat gene is localized on chromosome 14 and is coded by six exons mapped in region 14p22. When expressed in Xenopus laevis oocytes, Soat shows transport function for estrone-3-sulfate (Km = 31 microM, Vmax = 5557 fmol/oocyte/30 min) and dehydroepiandrosterone sulfate (Km = 30 microM, Vmax = 5682 fmol/oocyte/30 min). Soat does not transport taurocholate, estradiol-17beta-glucuronide, nor ouabain.
Asunto(s)
Glándulas Suprarrenales/química , Estrona/análogos & derivados , Transportadores de Anión Orgánico Sodio-Dependiente/genética , Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Transportadores de Anión Orgánico/genética , Transportadores de Anión Orgánico/metabolismo , Secuencia de Aminoácidos , Animales , Transporte Biológico , Clonación Molecular , Sulfato de Deshidroepiandrosterona/metabolismo , Estrona/metabolismo , Componentes del Gen , Datos de Secuencia Molecular , Oocitos/metabolismo , Transportadores de Anión Orgánico/química , Transportadores de Anión Orgánico Sodio-Dependiente/química , Estructura Terciaria de Proteína , Ratas , Alineación de Secuencia , Distribución Tisular , Xenopus laevisRESUMEN
O presente trabalho teve como objetivo quantificar o grau de melhora da força de preensão palmar nos pacientes hansenianos com seqüelas da mão. Trata-se de um estudo de caso com um paciente portador de hanseníase e o instrumento utilizado na coleta de dados foi o dinamômetro Jamar® que esteve auxiliando o estudo antes e depois da neurólise dos nervos ulnar e mediano. Concluiu-se com este estudo que o dinamômetro Jamar® é um instrumento confiável e seguro para detectar a perda da força de preensão palmar de uma pessoa e, para precisão dos resultados, padroniza-se a manopla do aparelho na posição 2 (dois) e a posição do paciente, sempre alternando os membros com intervalo de um minuto para evitar fadiga muscular. A neurólise é eficaz para liberar o nervo e, após este procedimento cirúrgico, utiliza-se tala gessada no membro e, posteriormente inicia-se a reabilitação. É através da Fisioterapia que o paciente consegue maior recuperação e mobilidade do membro afetado
Asunto(s)
Humanos , Masculino , Adulto , Lepra/rehabilitación , Lepra/terapia , Neuropatías CubitalesRESUMEN
O presente trabalho teve como objetivo quantificar o grau de melhora da força de preensão palmar nos pacientes hansenianos com sequelas da mão. Trata-se de um estudo de caso com um paciente portador de hanseníase e o instrumento utilizado na coleta de dados foi o dinamômetro Jamar que esteve auxiliando o estudo antes e depois da neurólise dos nervos ulnar e mediano. Conclui-se com este estudo que o dinamômetro Jamar é um instrumento confiável e seguro para detectar a perda da força de preensão palmar de uma pessoa e, para precisão dos resultados, padroniza-se a manopla do aparelho na posição 2 e a posição do paciente, sempre alternando os membros com intervalo de um minuto para evitar fadiga muscular. A neurólise é eficaz para liberar o nervo e, após este procedimento cirúrgico, utiliza-se tala gessada no membro e, posteriormente inicia-se a reabilitação. É através da Fisioterapia que o paciente consegue maior recuparação e mobilidade do membro afetado