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1.
Int J Mol Sci ; 21(13)2020 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-32605223

RESUMO

In Duchenne muscular dystrophy (DMD), the activation of proinflammatory and metabolic cellular pathways in skeletal muscle cells is an inherent characteristic. Synthetic glucocorticoid intake counteracts the majority of these mechanisms. However, glucocorticoids induce burdensome secondary effects, including hypertension, arrhythmias, hyperglycemia, osteoporosis, weight gain, growth delay, skin thinning, cushingoid appearance, and tissue-specific glucocorticoid resistance. Hence, lowering the glucocorticoid dosage could be beneficial for DMD patients. A more profound insight into the major cellular pathways that are stabilized after synthetic glucocorticoid administration in DMD is needed when searching for the molecules able to achieve similar pathway stabilization. This review provides a concise overview of the major anti-inflammatory pathways, as well as the metabolic effects of glucocorticoids in the skeletal muscle affected in DMD. The known drugs able to stabilize these pathways, and which could potentially be combined with glucocorticoid therapy as steroid-sparing agents, are described. This could create new opportunities for testing in DMD animal models and/or clinical trials, possibly leading to smaller glucocorticoids dosage regimens for DMD patients.


Assuntos
Anti-Inflamatórios/farmacologia , Glucocorticoides/farmacologia , Músculo Esquelético/efeitos dos fármacos , Distrofia Muscular de Duchenne/tratamento farmacológico , Esteroides/metabolismo , Animais , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/patologia
3.
Neuromuscul Disord ; 22(1): 26-33, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21855341

RESUMO

Heat shock proteins are important factors in skeletal muscle physiology and stress response. We examined the effects of chronic inflammation on the distribution of heat shock protein families 70 and 90 using immunofluorescence and Western blotting, in muscle biopsies from 33 idiopathic inflammatory myopathy patients [aged 26-66 (dermatomyositis), 17-78 (polymyositis) and 57-80 (sporadic inclusion body myositis) years], and seven Duchenne muscular dystrophy patients (aged 3-19 years). Our results reveal the multifaceted role played by chaperones in inflammatory muscle tissue. On the one hand, regenerating, atrophic and vacuolated muscle fibers displayed upregulation of both protein families. Higher levels of chaperones in challenged fibers point to the myocyte's attempt to restore and regenerate. On the other hand, heat shock proteins of the 90 family were strongly upregulated in macrophages and cytotoxic T-cells actively invading nonnecrotic muscle fibers of sporadic inclusion body myositis and polymyositis, probably conferring enhanced myocytotoxic capacity. Our data provide positive arguments for exploring heat shock protein 90-based therapy in inflammatory muscle disease.


Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Distrofia Muscular de Duchenne/metabolismo , Miosite/metabolismo , Miosite/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Dermatomiosite/metabolismo , Dermatomiosite/patologia , Feminino , Humanos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Distrofia Muscular de Duchenne/patologia , Miosite de Corpos de Inclusão/metabolismo , Miosite de Corpos de Inclusão/patologia , Polimiosite/metabolismo , Polimiosite/patologia , Linfócitos T/metabolismo , Linfócitos T/patologia
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