Papel De Las Poliaminas En La Transducción De Señales Intracelulares: Posibles Proyecciones De Uso Clínico En El Manejo De Las Distrofias Musculares Por Medio De Su Inhibición Con DMFO.
[Papel De Las Poliaminas En La Transducción De Señales Intracelulares: Posibles Proyecciones De Uso Clínico En El Manejo De Las Distrofias Musculares Por Medio De Su Inhibición Con DMFO.]Enrique Daniel Austin-Ward1
1. CAJA DE SEGURO SOCIAL;
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Resumen
[Polyamines role in intracellular signals transduction: possible projections for clinical use in muscular dystrophies’ management through its inhibition with difluoromethylornithine]
Resumen
Las distrofias musculares de origen genético son muy diversas y, tanto su diagnóstico preciso como su manejo, suponen un reto importante. En cuanto a este último aspecto, no obstante el desarrollo en proceso de nuevas estrategias a nivel molecular para su tratamiento, las herramientas con que se cuenta para este propósito son limitadas, y pocas veces pueden influir de manera efectiva para evitar el deterioro progresivo que muchos de estos pacientes experimentan. Además, las terapias de última generación no abarcan la gran diversidad de estas patologías y no se espera que estén disponibles a corto plazo para la mayoría de los pacientes.
El propósito del artículo es mostrar el papel de las poliaminas, actores ubicuos en el metabolismo intracelular tal vez poco conocidos; cómo están involucrados en los procesos fisiológicos y patológicos, y cómo también pudiesen estar involucrados en la fisiopatología de las distrofias musculares. Su inhibición controlada, mediante Difluorometilornitina (DFMO), pudiese constituir un mecanismo para enlentecer o eliminar el deterioro muscular de estos pacientes, al utilizarse como una herramienta dentro del arsenal de las ya existentes.
Abstract
Muscular dystrophies of genetic origin are very diverse and, both their precise diagnosis and their management represent an important challenge. Regarding this last aspect, despite the development in process of new strategies at the molecular level for its treatment, the tools available for this purpose are limited, and can rarely influence effectively to avoid the progressive deterioration that many of these patients experience. In addition, the latest-generation therapies do not cover the great diversity of these pathologies and are not expected to be available in the short term for most patients.
The purpose of the article is to show the role of polyamines, ubiquitous actors in intracellular metabolism, perhaps little known; how they are involved in physiological and pathological processes, and how they could also be involved in the physiopathology of muscular dystrophies. Its controlled inhibition, by difluoromethylilitin (DFMO), could be a mechanism to slow or eliminate the muscle deterioration of these patients, by being used as a tool within the arsenal of those already existing.
Abstract
[Polyamines role in intracellular signals transduction: possible projections for clinical use in muscular dystrophies’ management through its inhibition with difluoromethylornithine]
Resumen
Las distrofias musculares de origen genético son muy diversas y, tanto su diagnóstico preciso como su manejo, suponen un reto importante. En cuanto a este último aspecto, no obstante el desarrollo en proceso de nuevas estrategias a nivel molecular para su tratamiento, las herramientas con que se cuenta para este propósito son limitadas, y pocas veces pueden influir de manera efectiva para evitar el deterioro progresivo que muchos de estos pacientes experimentan. Además, las terapias de última generación no abarcan la gran diversidad de estas patologías y no se espera que estén disponibles a corto plazo para la mayoría de los pacientes.
El propósito del artículo es mostrar el papel de las poliaminas, actores ubicuos en el metabolismo intracelular tal vez poco conocidos; cómo están involucrados en los procesos fisiológicos y patológicos, y cómo también pudiesen estar involucrados en la fisiopatología de las distrofias musculares. Su inhibición controlada, mediante Difluorometilornitina (DFMO), pudiese constituir un mecanismo para enlentecer o eliminar el deterioro muscular de estos pacientes, al utilizarse como una herramienta dentro del arsenal de las ya existentes.
Abstract
Muscular dystrophies of genetic origin are very diverse and, both their precise diagnosis and their management represent an important challenge. Regarding this last aspect, despite the development in process of new strategies at the molecular level for its treatment, the tools available for this purpose are limited, and can rarely influence effectively to avoid the progressive deterioration that many of these patients experience. In addition, the latest-generation therapies do not cover the great diversity of these pathologies and are not expected to be available in the short term for most patients.
The purpose of the article is to show the role of polyamines, ubiquitous actors in intracellular metabolism, perhaps little known; how they are involved in physiological and pathological processes, and how they could also be involved in the physiopathology of muscular dystrophies. Its controlled inhibition, by difluoromethylilitin (DFMO), could be a mechanism to slow or eliminate the muscle deterioration of these patients, by being used as a tool within the arsenal of those already existing.
Citas
[1] Visek WJ. Arginine needs physiological state and usual diets. A reevaluation. J Nutr 1986;116(1):36-46
[2] Canellakis ZN, Marsh LL, Bondy PK. Polyamines and their derivatives as modulators in growth and differentiation. Yale J Bio Med 1989; 62(5):481-91.
[3] Mathy C, Carlier P, Yerna N, Rorive G. Polyamines and cardiovascular hypertrophy in experimental hypertension. Arch Mal Coeur Vaiss 1987; 80(6):777-82.
[4] Le Petit J, Nobili O, Boyer J. Simulation of brain lipase activity by polyamines. Comparison with the effect of ACTH. Pharmacol Biochem Beba 1986; 24(6): 1543-5.
[5] Huang LC, Chang LY. Stimulation of muscle glycogen synthase phosphatase by polyamines. Biochim Biophys Acta 1980; 613(1):106-15.
[6] Smirnov IV, Dimitrov SI, Makarov VL. Interaction of polyamines with chromatin and DNA: formation of compact structures. Mol biol (Mosk) 1987; 21(5):1411-21.
[7] Hougaard DM, Del Castillo AM, Larsson LI. Endogenous polyamines associate with DNA during its condensation in mammalian tissue. A fluorescence cytochemical and immnocytochemical study on polyamines in fetal rat liver. Eur J Cell Biol 1988: 45(2):311-4
[8] Anderson PJ, Bardocz S, Campos R, Brown DL. The effect of polyamines on tubulin assembly. Biochem Biophys Res Commun 1985; 132(1):147-54.
[9] Grant NJ, Oriol-Audit C, Dickens MJ. Supramolecular forms of actin induced by polyamines; and electron microscopic study. Eur J Cell Biol 1983; 30(1):67-73.
[10] Koenig H, Goldstone AD, Lu CY. Polyamines are intracellular messengers in the beta-adrenergic regulation of Ca2+ fluxes, (Ca2+i) and membrane transport in rat heart myocytes. Biochem Biophys Res Comun 1988; 153(3):1179-85
[11] Kohno H, Sasaki K, Yamaguchi M, Ohkubo Y. Spermine modulates calcium flux through the rat erythrocyte membrane. Biol Pharm Bull 1997; 20(2):153-7.
[12] Ventura C, Ferroni C, Flamigni F, Stefanelli C, Capogrossi MC. Polyamine effects on (Ca2+i) homeostasis and contractility in isolated rat ventricular cardiomyocytes. Am J Physiol 1994; 267(2Pt2):H587-92.
[13] McMillin-Wood J, Wolkowicz PE, Chu A, Tate CA, Goldstein MA, Entman ML. Calcium uptake by two preparations of mitochondria from heart. Biochim Biophys Act 1980; 591(2):251-65.
[14] Rustenbeck I, Eggers G, Munster W, Lenzen S. Effect of spermine on mitochondrial matrix calcium in relation to its enhancement of mitochondrial calcium uptake. Biochem Biophys Res Común 1993; 194(3):1261-8.
[15] Rottemberg H, Marbach M. Regulation of Ca2+ transport in brain mitochondria. I. The mechanism of spermine enhancement of Ca2+ uptake and retention. Biochim Biophys Acta 1990; 1016(1):77-86.
[16] Ginty DD, Seidel ER. Polyamine-dependent growth and calmodulin-regulated induction of ornithine decarboxylase. Am J Physiol 1989; 256(2Pt1):G342-8.
[17] Smith CD, Snyderman R. Modulation of inositol phospholipid metabolism by polyamines. Biochem J 1988; 256:125-130.
[18] Bueb J-L, Da Silva A, Mousli M, Landry Y. Natural polyamines stimulate G-proteins. Biochem J 1992; 282:545-550.
[19] Huang C, Liang NC. Increase in cytoskeletal actin induced by inositol 1,4-bisphosphate in saponin-permated pig platelets. Cell Biol Int 1994; 18(8):797-804.
[20] Zarka A, Shoshan-Barmatz V. The interaction of spermine with the ryanodine receptor from skeletal muscle. Biochim Biophys Acta 1992; 1108(1):13-20.
[21] Hayase R, Eguchi K, Sekiba K. Polyamine levels in gynecologic malignancies. Acta Med Okayama 1985; 39(1):35-45.
[22] Mollica F, Li Volti S, Rapisarda A, Longo G, Pavone L, Vanella A. Increased erythrocyte spermine in Duchenne muscular dystrophy. Pediatr Res 1980; 14:1196-1198.
[23] Russell DH, Stern LZ. Altered polyamine excretion in Duchenne muscular dystrophy. Neurology 1981; 31:80-83.
[24] Szathmary I, Selmeci L, Szobor A, Molnar J. Altered polyamine levels in skeletal muscle of patients with myasthenia gravis. Clin Neuropathol 1994;13(4):181-4
[25] Hoedemaekers AC, van BredaVriesman PJ, De Baets MH. Myasthenia gravis as a prototype autoinmune receptor disease. Immunol Res 1997; 16(4):341-54.
[26] Dubowitz V. The Muscular Dystrophies. En: Muscle Disorders in Childhood. 2da Edición. WB Saunders Company. Londres. 1995. Págs.: 34-65.
[27] Robbins SL, Cotran KS, Kumar V. Distrofias Musculares. En: Patología Estructural y Funcional. 3ra Edición. Nueva Editorial Interamericana. México 1988 Pág. 1284.
[28] Camina F, Novo-Rodríguez MI, Rodríguez-Segade S, Castro-Gago M. Purine and carnitine metabolism in muscle of patients with Duchenne muscular dystrophy. Clin Chim Act 1995; 243: 151-164. Published erratum appears in Clin Chim Act 1996 15; 252:105.
[29] Frass M, Toifl K, Leixnering W. Adenine metabolism in erythrocytes of patients with Duchenne muscular dystrophy. Eur Neurol 1983;22(5):380-4.
[30] Kemp GJ, Taylor Dj; Dunn JF, Frostick SP, Radda GK. Cellular energetics of dystrophic muscle. J Neurol Sci 1993; 116(2):201-6.
[31] Marks AR. Intracellular calcium-release channels: regulators of cell life and death. Am J Physiol 1997; 272:H597-605.
[32] Robert V, Massimino ML, Tosello V, Marsault R, Cantini M, Sorrentino V, Pozzan T. Alteration in calcium handling at the subcellular level in mdx myotubes. J Biol Chem 2000(epub ahead of print).
[33] Kuznetsov AV, Winkler K, Wiedemann FR, von Bossanyi P, Dietzmann K, Kunz WS. Impaired mitochondrial oxidative phosphorylation in skeletal muscle of the dystrophin-deficient mdx mouse. Mol Cell Biochem 1998; 183(1-2):87-96.
[34] Poole-Wilson PA, Harding DP, Bourdillon PD, Tones MA. Calcium out of control. J Mol Cell Cardiol 1984; 16(2):175-87.
[35] Touraki M, Beis I. Alterations in the energy metabolism of the isolated perfused frog heart during calcium depletion and subsequent repletion. J Comp Physiol (B) 1991; 161(1):85-92.
[36] Ziegelhoffer A, Ravingerova T, Tribulova N, Slezak J, Okolicay J, Tregerova V, Kruse EG, Bartel S. Partial prevention of calcium paradox in isolated perfused rat hearts by diltiazem. Biomed Biochim Acta 1989; 48(2-3):S96-101.
[37] Bhattacharya SK, Johnson PL, Thakar JH. Reversal of impaired oxidative phosphorylation and calcium overloading in the skeletal muscle mitochondria of CHF-146 dystrophic hamsters. Mol Chem Neuropathol 1998; 34(1):53-77.
[38] Koenig H, Goldstone AD, Trout JJ, Lu CY. Polyamines mediate uncontrolled calcium entry and cell damage in rat heart in the calcium paradox. J Clin Invest 1987; 80(5):1322-31.
[39] He Y, Kashiwagi K, Fukuchi J, Terao K, Shirahata A, Igarashi K. Correlation between the inhibition of cell growth by accumulated polyamines and the decrease of magnesium and ATP. Eur J Biochem. 1993 Oct 1; 217(1):89-96.
[40] Sjöholm A, Welsh N, Hoftiezer V, Bankston PW, Hellerström C. Increased glucose oxidation and contents of insulin and ATP in polyamine-depleted rat insulinoma cells (RINm5F). Biochem J. 1991 Jul 15; 277 ( Pt 2):533-40.
[41] Estrada M, Liberona JL, Miranda M, Jaimovich E. Aldosterone and testosterone mediated intracellular calcium response in skeletal muscle Cell cultures. Am J Physiol Endocrinol Metab. 2000;279(1):E132-9.
[42] Liberona JL, Powell JA, Shenoi S, Petherbridge L, Caviedes R, Jaimovich E. Differnces in both inositol 1,4,5-triphosphate mass and inositol 1,4,5-triphosphate receptors between normal and dystrophic skeletal muscle cell lines. Muscle Nerve 1998; 21:902-909.
[43] Kliegman RM, Stanton BF, St Geme III JW, Schor NF, Behrmam RE. Duchenne and Becker Muscular Dystrophies. En: Nelson Textbook of Pediatrics. 20th Edition 2016. Editorial Elsevier. Tomo 2do. Págs.: 2976-2979.
[44] Kole R, Krieg AM. Exon skipping therapy for Duchenne Muscular Dystrophy. Adv Drug Deliv Rev. 2015 Jun 29; 87:104-7.
[45] Shimizu-Motohashi Y, Komaki H, Motohashi N, Takeda S, Yokota T, Aoki Y. Restoring Dystrophin Expression in Duchenne Muscular Dystrophy: Current Status of Therapeutic Approaches. J Pers Med. 2019 Jan 7; 9(1). pi: E1
[46] Wang JZ, Wu P, Shi ZM, Xu YL, Liu ZJ. The AAV-mediated and RNA-guided CROS´R/Cas9 system for gene therapy of DMD and BMD. Brain Dev 2017Aug, 39(7):547-556.
[47] Wakefield PM, Tinsley JM, Wood MJ, Gilbert R, Karpati G, Davies KE. Prevention of the dystrophic phenotype in dystrophin/utrophin-deficient muscle following adenovirus-mediated transfer of a utrophin minigene. Gene Ther 2000; 7(3):201-4.
[48] McCann PP, Bacchi CJ, Clarkson AB Jr, Seed Jr, Nathan HC, Amole BO, Hutner SH, Sjoerdsma A. Further studies on difluoromethylornithine in African trypanosomes. Med Biol 1981:59(5-6):434-40
[49] Kumar A, Naguib YW, Shi YC, Cui Z. A method to improve the efficacy of topical eflornithine hydrochloride cream. Drug Deliv. 2016 Jun; 23(5):1495-501.
[50] Gutiérrez LG, Hernández-Morales M, Núñez L, Villalobos C. Inhibition of Polyamine Biosynthesis ReversesCA3+ Channel Remodeling in Colon Cancer Cells. Cancers (Basel). 2019 Jan 13; 11(1). pii: E83.
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