Disciplina Discipline RFI5797
Controle Neural e Hormonal da Massa Muscular Esquelética
Neural and Hormonal Control of Skeletal Muscle Mass

Área de Concentração: 17134

Concentration area: 17134

Criação: 04/06/2024

Creation: 04/06/2024

Ativação: 04/06/2024

Activation: 04/06/2024

Nr. de Créditos: 3

Credits: 3

Carga Horária:

Workload:

Docentes Responsáveis:

Professors:

Isis do Carmo Kettelhut

Luiz Carlos Carvalho Navegantes

Objetivos:

Fornecer ao aluno conhecimento teórico-prático sobre os principais modelos experimentais e metodologias disponíveis para o estudo da regulação neuroendócrina da massa corporal, concentrando-se para isso na musculatura esquelética. Apresentar em aulas teóricas e discutir em seminários tópicos de conhecimento avançado sobre o controle do metabolismo de proteínas na musculatura esquelética, em situações fisiológicas e patológicas. Analisar e discutir, em aulas práticas, os resultados dos experimentos à luz dos conceitos mais modernos da área da endocrinologia e metabolismo, dando-se ênfase ao papel fisiológico de hormônios e do sistema nervoso central na manutenção da massa magra.

Objectives:

Provide the student with theoretical-practical knowledge about the main experimental models and methodologies available for the study of the neuroendocrine regulation of body mass, focusing on skeletal muscles. Present in theoretical classes and discuss in seminars advanced knowledge topics on the control of protein metabolism in skeletal muscles, in physiological and pathological situations. Analyze and discuss, in practical classes, the results of experiments in light of the most modern concepts in the area of endocrinology and metabolism, with emphasis on the physiological role of hormones and the central nervous system in maintaining lean mass.

Justificativa:

A disponibilidade de uma nova disciplina específica na área de Metabolismo no “Programa de Pós-graduação em Fisiologia” da FMRP-USP contribuirá para a formação teórica e científica de nossos alunos em um dos segmentos da Fisiologia ainda pouco discutidos neste programa. O curso oferecido justifica-se não só pelo aprendizado dos mecanismos básicos de controle do metabolismo de proteínas em situações fisiológicas, mas também pela melhor compreensão da base fisiopatológica de doenças debilitantes que levam à perda de massa magra. Alunos da Fisiologia e de outras áreas de concentração, interessados na importância fisiológica da manutenção da massa muscular, poderão se beneficiar desses novos conhecimentos em seus projetos de pesquisa e para a elaboração de futuros trabalhos.

Rationale:

The availability of a new specific discipline in the area of Metabolism in the “Postgraduate Program in Physiology” at FMRP-USP will contribute to the theoretical and scientific training of our students in one of the segments of Physiology that is still little discussed in this program. The course offered is justified not only by learning the basic mechanisms for controlling protein metabolism in physiological situations, but also by better understanding the pathophysiological basis of debilitating diseases that lead to the loss of lean mass. Students of Physiology and other areas of concentration, interested in the physiological importance of maintaining muscle mass, will be able to benefit from this new knowledge in their research projects and for the preparation of future work.

Conteúdo:

O curso constará de 2 aulas teóricas acompanhadas de 10 seminários para discussão de trabalhos clássicos e atuais sobre a regulação dos processos de síntese e degradação de proteínas musculares em situações fisiológicas e patológicas, dando-se ênfase ao papel do sistema proteolítico ubiquitina-proteassoma, sistema lisossomal e sistema proteolítico dependente de cálcio. Haverá ainda 1 aula prática, onde o aluno terá a oportunidade de familiarizar-se com diferentes metodologias utilizadas para o estudo do metabolismo protéico e modelos experimentais de atrofia muscular. PROGRAMA ENCONTRO 1: Formação dos grupos e distribuição das separatas. Aula teórica: -Características anátomo-fisiológicas da musculatura esquelética -Aspectos gerais do balanço de proteínas musculares e dos métodos de estudo. Leitura básica para todos: -Gilda JE et al. Proteasome gene expression is controlled by coordinated functions of multiple transcription factors. J Cell Biol. 2024 Aug 5;223(8): e202402046. ENCONTRO 2: Prática demonstrativa de métodos e modelos experimentais para o estudo do metabolismo de proteínas: -Músculos isolados: Identificação, remoção, pesagem e incubação de músculos soleus e EDL de animais diabéticos, tratados com dexametasona e com desnervação atrófica (secção do nervo ciático). -Eletroporação: Técnica de transfeção gênica em músculo esquelético (Tibial anterior) de camundongos normais in vivo. Leitura Complementar: Murakami T, Sunada Y. Plasmid DNA Gene Therapy by Electroporation: Principles and Recent Advances. Curr Gene Ther. 2011 Dec 1;11(6):447–56. ENCONTRO 3: Seminários 1: Controle hormonal do sistema proteolítico ubiquitina-proteassoma Seminário 1a: -Goldberg AL et al. Mechanisms that Activate 26S Proteasomes and Enhance Protein Degradation. Biomolecules. 2021 May 22;11(6):779. Leitura complementar: -Price SR, Bailey JL, Wang X, Jurkovitz C, England BK, Ding X, Phillips LS, Mitch WE. Muscle wasting in insulinopenic rats results from activation of the ATP-dependent, ubiquitin-proteasome proteolytic pathway by a mechanism including gene transcription. J Clin Invest 98(8):1703-8, 1996. Seminário 1b: Silveira WA et al. cAMP-dependent protein kinase inhibits FoxO activity and regulates skeletal muscle plasticity in mice. FASEB J. 2020 Sep;34(9):12946-12962. Leitura complementar: -Combaret L, Taillandier D, Dardevet D, Bechet D, Ralliere C, Claustre A, Grizard J, Attaix D. Glucocorticoids regulate mRNA levels for subunits of the 19 S regulatory complex of the 26 S proteasome in fast-twitch skeletal muscles. Biochem J. 378(Pt 1):239-46, 2004. ENCONTRO 4: Seminários 2: Ubiquitina ligases e vias de sinalizações envolvidas na atrofia e hipertrofia muscular Seminário 2a: -Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 23: 294(5547):1704-8, 2001. -Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A. 4: 98(25):14440-5, 2001. Leitura complementar: Hughes DC et al. A critical discussion on the relationship between E3 ubiquitin ligases, protein degradation, and skeletal muscle wasting: it's not that simple. Am J Physiol Cell Physiol. 2023 Dec 1;325(6):C1567-C1582. Seminário 2b: -Stitt TN, Drujan D, Clarke BA, Panaro F, Timofeyva Y, Kline WO, Gonzalez M,Yancopoulos GD, Glass DJ. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell 7:14(3): 395-403, 2004. Graça et al. Epinephrine depletion exacerbates the fasting-induced protein breakdown in fast-twitch skeletal muscles. Am J Physiol Endocrinol Metab. 305(12): E1483-94, 2013. Leitura complementar: Gonçalves et al. Insulin/IGF1 signaling mediates the effects of beta2-adrenergic agonists on muscle proteostasis and growth. JCSM v. 10 (2), p. 455-475, 2019. ENCONTRO 5: Seminários 3: Sistema proteolítico lisossomal/autofágico Seminário 3a: Leduc-Gaudet JP et al. MYTHO is a novel regulator of skeletal muscle autophagy and integrity. Nat Commun. 2023 Mar 2;14(1):1199. Seminário 3b: Milan et al. Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy. Nat Commun.10 (6): 6670, 2015. Leitura básica para os dois seminários: Franco-Romero A, Sandri M. Role of autophagy in muscle disease. Mol Aspects Med. 2021 Dec;82:101041. doi: 10.1016/j.mam.2021.101041. ENCONTRO 6: Seminários: Sistema proteolítico dependente de cálcio Seminário 4a: -Williams AB, Decourten-Myers GM, Fischer JE, Luo G, Sun X, Hasselgren PO. Sepsis stimulates release of myofilaments in skeletal muscle by a calcium-dependent mechanism. FASEB J 13(11):1435-43, 1999. Leitura complementar: Wei W, Fareed MU, Evenson A, Menconi MJ, Yang H, Petkova V, Hasselgren PO. Sepsis stimulates calpain activity in skeletal muscle by decreasing calpastatin activity but does not activate caspase-3. Am J Physiol Regul Integr Comp Physiol 288(3): R580-90, 2005. Seminário 4b: Machado J et al. α-Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles. Mol Metab. 2019 Oct;28:91-106. doi: 10.1016/j.molmet.2019.06.024. Leitura básica para os dois seminários: -Costelli P, Reffo P, Penna F, Autelli R, Bonelli G, Baccino FM. Ca2+-dependent proteolysis in muscle wasting. Int J Biochem Cell Biol 37(10): 2134-46, 2005. Review. ENCONTRO 7: Seminários: Síntese Proteica Seminário 5a: Rodriguez J, Vernus B, Chelh I, Cassar-Malek I, Gabillard JC, Hadj Sassi A, Seiliez I, Picard B, Bonnieu A. Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways. Cell Mol Life Sci. 71 (22): 4361-71, 2014. Seminário 5b: Lautherbach N et al. Urocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathways. Mol Metab. 2022 Jun;60:101492. doi: 10.1016/j.molmet.2022.101492. Leitura complementar: Francaux M, Deldicque L. Exercise and the control of muscle mass in human. Pflugers Arch. 471(3):397-411, 2019. ENCONTRO 8: Avaliação Geral

Content:

The course will consist of 2 theoretical classes accompanied by 10 seminars to discuss classic and current works on the regulation of muscle protein synthesis and degradation processes in physiological and pathological situations, with emphasis on the role of the ubiquitin-proteasome proteolytic system, a system lysosomal and calcium-dependent proteolytic system. There will also be 1 practical class where the students can familiarize themselves with different methodologies used to study protein metabolism and experimental models of muscular atrophy. PROGRAM MEETING 1: Formation of groups and distribution of separates. Theoretical class: -Anatomo-physiological characteristics of skeletal muscles -General aspects of muscle protein balance and study methods. Basic reading for everyone: -Gilda JE et al. Proteasome gene expression is controlled by coordinated functions of multiple transcription factors. J Cell Biol. 2024 Aug 5;223(8): e202402046. MEETING 2: Demonstrative practice of experimental methods and models for the study of protein metabolism: -Isolated muscles: Identification, removal, weighing and incubation of soleus and EDL muscles from diabetic animals, treated with dexamethasone and with atrophic denervation (section of the sciatic nerve). -Electroporation: Gene transfection technique in skeletal muscle (Tibialis anterior) of normal mice in vivo. Additional Reading: Murakami T, Sunada Y. Plasmid DNA Gene Therapy by Electroporation: Principles and Recent Advances. Curr Gene Ther. 2011 Dec 1;11(6):447–56. MEETING 3: Seminars 1: Hormonal control of the ubiquitin-proteasome proteolytic system Seminar 1a: -Goldberg AL et al. Mechanisms that Activate 26S Proteasomes and Enhance Protein Degradation. Biomolecules. 2021 May 22;11(6):779. Additional Reading: -Price SR, Bailey JL, Wang X, Jurkovitz C, England BK, Ding X, Phillips LS, Mitch WE. Muscle wasting in insulinopenic rats results from activation of the ATP-dependent, ubiquitin-proteasome proteolytic pathway by a mechanism including gene transcription. J Clin Invest 98(8):1703-8, 1996. Seminar 1b: Silveira WA et al. cAMP-dependent protein kinase inhibits FoxO activity and regulates skeletal muscle plasticity in mice. FASEB J. 2020 Sep;34(9):12946-12962. Additional Reading: -Combaret L, Taillandier D, Dardevet D, Bechet D, Ralliere C, Claustre A, Grizard J, Attaix D. Glucocorticoids regulate mRNA levels for subunits of the 19 S regulatory complex of the 26 S proteasome in fast-twitch skeletal muscles. Biochem J. 378(Pt 1):239-46, 2004. MEETING 4: Seminars 2: Ubiquitin ligases and signaling pathways involved in muscle atrophy and hypertrophy Seminar 2a: -Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 23: 294(5547):1704-8, 2001. -Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A. 4: 98(25):14440-5, 2001. Additional Reading: Hughes DC et al. A critical discussion on the relationship between E3 ubiquitin ligases, protein degradation, and skeletal muscle wasting: it's not that simple. Am J Physiol Cell Physiol. 2023 Dec 1;325(6):C1567-C1582. Seminar 2b: -Stitt TN, Drujan D, Clarke BA, Panaro F, Timofeyva Y, Kline WO, Gonzalez M,Yancopoulos GD, Glass DJ. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell 7:14(3): 395-403, 2004. - Graça et al. Epinephrine depletion exacerbates the fasting-induced protein breakdown in fast-twitch skeletal muscles. Am J Physiol Endocrinol Metab. 305(12): E1483-94, 2013. Additional Reading: Gonçalves et al. Insulin/IGF1 signaling mediates the effects of beta2-adrenergic agonists on muscle proteostasis and growth. JCSM v. 10 (2), p. 455-475, 2019. MEETING 5: Seminars 3: Lysosomal/autophagic proteolytic system Seminar 3a: Leduc-Gaudet JP et al. MYTHO is a novel regulator of skeletal muscle autophagy and integrity. Nat Commun. 2023 Mar 2;14(1):1199. Seminar 3b: Milan et al. Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy. Nat Commun.10 (6): 6670, 2015. Basic reading for both seminars: Franco-Romero A, Sandri M. Role of autophagy in muscle disease. Mol Aspects Med. 2021 Dec;82:101041. doi: 10.1016/j.mam.2021.101041. MEETING 6: Seminars: Calcium-dependent proteolytic system Seminar 4a: -Williams AB, Decourten-Myers GM, Fischer JE, Luo G, Sun X, Hasselgren PO. Sepsis stimulates release of myofilaments in skeletal muscle by a calcium-dependent mechanism. FASEB J 13(11):1435-43, 1999. Additional Reading: Wei W, Fareed MU, Evenson A, Menconi MJ, Yang H, Petkova V, Hasselgren PO. Sepsis stimulates calpain activity in skeletal muscle by decreasing calpastatin activity but does not activate caspase-3. Am J Physiol Regul Integr Comp Physiol 288(3): R580-90, 2005. Seminar 4b: Machado J et al. α-Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles. Mol Metab. 2019 Oct;28:91-106. doi: 10.1016/j.molmet.2019.06.024. Basic reading for both seminars: -Costelli P, Reffo P, Penna F, Autelli R, Bonelli G, Baccino FM. Ca2+-dependent proteolysis in muscle wasting. Int J Biochem Cell Biol 37(10): 2134-46, 2005. Review. MEETING 7: Seminars: Protein Synthesis Seminar 5a: Rodriguez J, Vernus B, Chelh I, Cassar-Malek I, Gabillard JC, Hadj Sassi A, Seiliez I, Picard B, Bonnieu A. Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways. Cell Mol Life Sci. 71 (22): 4361-71, 2014. Seminar 5b: Lautherbach N et al. Urocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathways. Mol Metab. 2022 Jun;60:101492. doi: 10.1016/j.molmet.2022.101492. Additional Reading: Francaux M, Deldicque L. Exercise and the control of muscle mass in human. Pflugers Arch. 471(3):397-411, 2019. MEETING 8: General Assessment

Forma de Avaliação:

Freqüência, participação em seminários e prova teórica.

Type of Assessment:

Attendance, participation in seminars and theoretical test.

Bibliografia:

Gilda JE et al. Proteasome gene expression is controlled by coordinated functions of multiple transcription factors. J Cell Biol. 2024 Aug 5;223(8): e202402046. Goldberg AL et al. Mechanisms that Activate 26S Proteasomes and Enhance Protein Degradation. Biomolecules. 2021 May 22;11(6):779. Silveira WA et al. cAMP-dependent protein kinase inhibits FoxO activity and regulates skeletal muscle plasticity in mice. FASEB J. 2020 Sep;34(9):12946-12962. Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 23: 294(5547):1704-8, 2001. Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A. 4: 98(25):14440-5, 2001. Stitt TN, Drujan D, Clarke BA, Panaro F, Timofeyva Y, Kline WO, Gonzalez M,Yancopoulos GD, Glass DJ. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell 7:14(3): 395-403, 2004. Graça et al. Epinephrine depletion exacerbates the fasting-induced protein breakdown in fast-twitch skeletal muscles. Am J Physiol Endocrinol Metab. 305(12): E1483-94, 2013. Leduc-Gaudet JP et al. MYTHO is a novel regulator of skeletal muscle autophagy and integrity. Nat Commun. 2023 Mar 2;14(1):1199. Milan et al. Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy. Nat Commun.10 (6): 6670, 2015. Franco-Romero A, Sandri M. Role of autophagy in muscle disease. Mol Aspects Med. 2021 Dec;82:101041. doi: 10.1016/j.mam.2021.101041 Williams AB, Decourten-Myers GM, Fischer JE, Luo G, Sun X, Hasselgren PO. Sepsis stimulates release of myofilaments in skeletal muscle by a calcium-dependent mechanism. FASEB J 13(11):1435-43, 1999. Machado J et al. α-Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles. Mol Metab. 2019 Oct;28:91-106. doi: 10.1016/j.molmet.2019.06.024. Costelli P, Reffo P, Penna F, Autelli R, Bonelli G, Baccino FM. Ca2+-dependent proteolysis in muscle wasting. Int J Biochem Cell Biol 37(10): 2134-46, 2005. Review. Rodriguez J, Vernus B, Chelh I, Cassar-Malek I, Gabillard JC, Hadj Sassi A, Seiliez I, Picard B, Bonnieu A. Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways. Cell Mol Life Sci. 71 (22): 4361-71, 2014. Lautherbach N et al. Urocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathways. Mol Metab. 2022 Jun;60:101492. doi: 10.1016/j.molmet.2022.101492. Complementar Murakami T, Sunada Y. Plasmid DNA Gene Therapy by Electroporation: Principles and Recent Advances. Curr Gene Ther. 2011 Dec 1;11(6):447–56. Price SR, Bailey JL, Wang X, Jurkovitz C, England BK, Ding X, Phillips LS, Mitch WE. Muscle wasting in insulinopenic rats results from activation of the ATP-dependent, ubiquitin-proteasome proteolytic pathway by a mechanism including gene transcription. J Clin Invest 98(8):1703-8, 1996. Combaret L, Taillandier D, Dardevet D, Bechet D, Ralliere C, Claustre A, Grizard J, Attaix D. Glucocorticoids regulate mRNA levels for subunits of the 19 S regulatory complex of the 26 S proteasome in fast-twitch skeletal muscles. Biochem J. 378(Pt 1):239-46, 2004. Hughes DC et al. A critical discussion on the relationship between E3 ubiquitin ligases, protein degradation, and skeletal muscle wasting: it's not that simple. Am J Physiol Cell Physiol. 2023 Dec 1;325(6):C1567-C1582. Gonçalves et al. Insulin/IGF1 signaling mediates the effects of beta2-adrenergic agonists on muscle proteostasis and growth. JCSM v. 10 (2), p. 455-475, 2019. Wei W, Fareed MU, Evenson A, Menconi MJ, Yang H, Petkova V, Hasselgren PO. Sepsis stimulates calpain activity in skeletal muscle by decreasing calpastatin activity but does not activate caspase-3. Am J Physiol Regul Integr Comp Physiol 288(3): R580-90, 2005. Francaux M, Deldicque L. Exercise and the control of muscle mass in human. Pflugers Arch. 471(3):397-411, 2019.

Bibliography:

Gilda JE et al. Proteasome gene expression is controlled by coordinated functions of multiple transcription factors. J Cell Biol. 2024 Aug 5;223(8): e202402046. Goldberg AL et al. Mechanisms that Activate 26S Proteasomes and Enhance Protein Degradation. Biomolecules. 2021 May 22;11(6):779. Silveira WA et al. cAMP-dependent protein kinase inhibits FoxO activity and regulates skeletal muscle plasticity in mice. FASEB J. 2020 Sep;34(9):12946-12962. Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 23: 294(5547):1704-8, 2001. Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A. 4: 98(25):14440-5, 2001. Stitt TN, Drujan D, Clarke BA, Panaro F, Timofeyva Y, Kline WO, Gonzalez M,Yancopoulos GD, Glass DJ. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell 7:14(3): 395-403, 2004. Graça et al. Epinephrine depletion exacerbates the fasting-induced protein breakdown in fast-twitch skeletal muscles. Am J Physiol Endocrinol Metab. 305(12): E1483-94, 2013. Leduc-Gaudet JP et al. MYTHO is a novel regulator of skeletal muscle autophagy and integrity. Nat Commun. 2023 Mar 2;14(1):1199. Milan et al. Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy. Nat Commun.10 (6): 6670, 2015. Franco-Romero A, Sandri M. Role of autophagy in muscle disease. Mol Aspects Med. 2021 Dec;82:101041. doi: 10.1016/j.mam.2021.101041 Williams AB, Decourten-Myers GM, Fischer JE, Luo G, Sun X, Hasselgren PO. Sepsis stimulates release of myofilaments in skeletal muscle by a calcium-dependent mechanism. FASEB J 13(11):1435-43, 1999. Machado J et al. α-Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles. Mol Metab. 2019 Oct;28:91-106. doi: 10.1016/j.molmet.2019.06.024. Costelli P, Reffo P, Penna F, Autelli R, Bonelli G, Baccino FM. Ca2+-dependent proteolysis in muscle wasting. Int J Biochem Cell Biol 37(10): 2134-46, 2005. Review. Rodriguez J, Vernus B, Chelh I, Cassar-Malek I, Gabillard JC, Hadj Sassi A, Seiliez I, Picard B, Bonnieu A. Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways. Cell Mol Life Sci. 71 (22): 4361-71, 2014. Lautherbach N et al. Urocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathways. Mol Metab. 2022 Jun;60:101492. doi: 10.1016/j.molmet.2022.101492. Additional Murakami T, Sunada Y. Plasmid DNA Gene Therapy by Electroporation: Principles and Recent Advances. Curr Gene Ther. 2011 Dec 1;11(6):447–56. Price SR, Bailey JL, Wang X, Jurkovitz C, England BK, Ding X, Phillips LS, Mitch WE. Muscle wasting in insulinopenic rats results from activation of the ATP-dependent, ubiquitin-proteasome proteolytic pathway by a mechanism including gene transcription. J Clin Invest 98(8):1703-8, 1996. Combaret L, Taillandier D, Dardevet D, Bechet D, Ralliere C, Claustre A, Grizard J, Attaix D. Glucocorticoids regulate mRNA levels for subunits of the 19 S regulatory complex of the 26 S proteasome in fast-twitch skeletal muscles. Biochem J. 378(Pt 1):239-46, 2004. Hughes DC et al. A critical discussion on the relationship between E3 ubiquitin ligases, protein degradation, and skeletal muscle wasting: it's not that simple. Am J Physiol Cell Physiol. 2023 Dec 1;325(6):C1567-C1582. Gonçalves et al. Insulin/IGF1 signaling mediates the effects of beta2-adrenergic agonists on muscle proteostasis and growth. JCSM v. 10 (2), p. 455-475, 2019. Wei W, Fareed MU, Evenson A, Menconi MJ, Yang H, Petkova V, Hasselgren PO. Sepsis stimulates calpain activity in skeletal muscle by decreasing calpastatin activity but does not activate caspase-3. Am J Physiol Regul Integr Comp Physiol 288(3): R580-90, 2005. Francaux M, Deldicque L. Exercise and the control of muscle mass in human. Pflugers Arch. 471(3):397-411, 2019.

Tipo de oferecimento da disciplina:

Presencial

Class type:

Presencial