Scientific contributions - Bottinelli

We have given a relevant contribution to:

• (I)  the understanding that skeletal muscle heterogeneity and plasticity are mostly based on the eistence of myosin isoforms with different functional properties and on the changes in their relative distribution occurring in physiologic and pathologic conditions.  Major references:
  

Bottinelli R. (2001). Functional heterogeneity of mammalian single muscle fibres: do myosin isoforms tell the whole story? Pflugers Arch 443, 6-17.

Bottinelli R & Reggiani C. (2000). Human skeletal muscle fibres: molecular and functional diversity. Prog Biophys Mol Biol 73, 195-262.

Bottinelli R, Canepari M, Pellegrino MA & Reggiani C. (1996). Force-velocity properties of human skeletal muscle fibres: myosin heavy chain isoform and temperature dependence. J Physiol 495 ( Pt 2), 573-586.

Bottinelli R, Canepari M, Reggiani C & Stienen GJ. (1994). Myofibrillar ATPase activity during isometric contraction and isomyosin composition in rat single skinned muscle fibres. J Physiol 481 ( Pt 3), 663-675.

Bottinelli R, Betto R, Schiaffino S & Reggiani C. (1994). Unloaded shortening velocity and myosin heavy chain and alkali light chain isoform composition in rat skeletal muscle fibres. J Physiol 478 ( Pt 2), 341-349.

Bottinelli R, Schiaffino S & Reggiani C. (1991). Force-velocity relations and myosin heavy chain isoform compositions of skinned fibres from rat skeletal muscle. J Physiol 437, 655-672.

• (II)  the identification of the molecular mechanisms underlying myosin isoform functional diversity. Major references:
  

Capitanio M, Canepari M, Maffei M, Beneventi D, Monico C, Vanzi F, Bottinelli R & Pavone FS. (2012). Ultrafast force-clamp spectroscopy of single molecules reveals load dependence of myosin working stroke. Nature methods 9, 1013-1019.

Canepari M, Maffei M, Longa E, Geeves M & Bottinelli R. (2012). Actomyosin kinetic of pure fast and slow rat myosin isoforms studied by in vitro motility assay approach. Exp Physiol.

Canepari M, Pellegrino MA, D'Antona G & Bottinelli R. (2010). Skeletal muscle fibre diversity and the underlying mechanisms. Acta Physiol (Oxf) 199, 465-476.

Nyitrai M, Rossi R, Adamek N, Pellegrino MA, Bottinelli R & Geeves MA. (2006). What limits the velocity of fast-skeletal muscle contraction in mammals? J Mol Biol 355, 432-442.

Capitanio M, Canepari M, Cacciafesta P, Lombardi V, Cicchi R, Maffei M, Pavone FS & Bottinelli R. (2006). Two independent mechanical events in the interaction cycle of skeletal muscle myosin with actin. Proc Natl Acad Sci U S A 103, 87-92.

Weiss S, Rossi R, Pellegrino MA, Bottinelli R & Geeves MA. (2001). Differing ADP Release Rates from Myosin Heavy Chain Isoforms Define the Shortening Velocity of Skeletal Muscle Fibers. J Biol Chem 276, 45902-45908.

• (III)  the understanding of the cellular mechanisms underlying functional adaptation to exercise, aging and disuse. Major references:
  

Canepari M, Pellegrino MA, D'Antona G & Bottinelli R. (2010). Single muscle fiber properties in aging and disuse. Scand J Med Sci Sports 20, 10-19.

D'Antona G, Lanfranconi F, Pellegrino MA, Brocca L, Adami R, Rossi R, Moro G, Miotti D, Canepari M & Bottinelli R. (2006). Skeletal muscle hypertrophy and structure and function of skeletal muscle fibres in male body builders. J Physiol 570, 611-627.

Canepari M, Rossi R, Pellegrino MA, Orrell RW, Cobbold M, Harridge S & Bottinelli R. (2005). Effects of resistance training on myosin function studied by the in vitro motility assay in young and older men. J Appl Physiol 98, 2390-2395.

D'Antona G, Pellegrino MA, Adami R, Rossi R, Carlizzi CN, Canepari M, Saltin B & Bottinelli R. (2003). The effect of ageing and immobilization on structure and function of human skeletal muscle fibres. J Physiol 552, 499-511.

Harridge SD, Bottinelli R, Canepari M, Pellegrino M, Reggiani C, Esbjornsson M, Balsom PD & Saltin B. (1998). Sprint training, in vitro and in vivo muscle function, and myosin heavy chain expression. J Appl Physiol 84, 442-449.

• (IV) the analysis of the effect of stem cell, gene and pharmacological therapies on muscular dystrophy. Major references:
  

Tedesco FS, Gerli MF, Perani L, Benedetti S, Ungaro F, Cassano M, Antonini S, Tagliafico E, Artusi V, Longa E, Tonlorenzi R, Ragazzi M, Calderazzi G, Hoshiya H, Cappellari O, Mora M, Schoser B, Schneiderat P, Oshimura M, Bottinelli R, Sampaolesi M, Torrente Y, Broccoli V & Cossu G. (2012). Transplantation of Genetically Corrected Human iPSC-Derived Progenitors in Mice with Limb-Girdle Muscular Dystrophy. Sci Transl Med 4, 140ra189.

Tedesco FS, Hoshiya H, D'Antona G, Gerli MF, Messina G, Antonini S, Tonlorenzi R, Benedetti S, Berghella L, Torrente Y, Kazuki Y, Bottinelli R, Oshimura M & Cossu G. (2011). Stem cell-mediated transfer of a human artificial chromosome ameliorates muscular dystrophy. Sci Transl Med 3, 96ra78.

D'Antona G, Brocca L, Pansarasa O, Rinaldi C, Tupler R & Bottinelli R. (2007). Structural and functional alterations of muscle fibres in the novel mouse model of facioscapulohumeral muscular dystrophy. J Physiol 584, 997-1009.

Brunelli S, Sciorati C, D'Antona G, Innocenzi A, Covarello D, Galvez BG, Perrotta C, Monopoli A, Sanvito F, Bottinelli R, Ongini E, Cossu G & Clementi E. (2007). Nitric oxide release combined with nonsteroidal antiinflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapy. Proc Natl Acad Sci U S A 104, 264-269.

Benchaouir R, Meregalli M, Farini A, D'Antona G, Belicchi M, Goyenvalle A, Battistelli M, Bresolin N, Bottinelli R, Garcia L & Torrente Y. (2007). Restoration of human dystrophin following transplantation of exon-skipping-engineered DMD patient stem cells into dystrophic mice. Cell stem cell 1, 646-657.

Sampaolesi M, Blot S, D'Antona G, Granger N, Tonlorenzi R, Innocenzi A, Mognol P, Thibaud JL, Galvez BG, Barthelemy I, Perani L, Mantero S, Guttinger M, Pansarasa O, Rinaldi C, Cusella De Angelis MG, Torrente Y, Bordignon C, Bottinelli R & Cossu G. (2006). Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs. Nature 444, 574-579.

Denti MA, Rosa A, D'Antona G, Sthandier O, De Angelis FG, Nicoletti C, Allocca M, Pansarasa O, Parente V, Musaro A, Auricchio A, Bottinelli R & Bozzoni I. (2006). Body-wide gene therapy of Duchenne muscular dystrophy in the mdx mouse model. Proc Natl Acad Sci U S A 103, 3758-3763.

Torrente Y, Belicchi M, Sampaolesi M, Pisati F, Meregalli M, D'Antona G, Tonlorenzi R, Porretti L, Gavina M, Mamchaoui K, Pellegrino MA, Furling D, Mouly V, Butler-Browne GS, Bottinelli R, Cossu G & Bresolin N. (2004). Human circulating AC133(+) stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle. J Clin Invest 114, 182-195.

Sampaolesi M, Torrente Y, Innocenzi A, Tonlorenzi R, D'Antona G, Pellegrino MA, Barresi R, Bresolin N, De Angelis MG, Campbell KP, Bottinelli R & Cossu G. (2003). Cell therapy of alpha-sarcoglycan null dystrophic mice through intra-arterial delivery of mesoangioblasts. Science 301, 487-492.

• (V) the understanding that muscle fibers plasticity is a very complex phenomenon which cannot be simply accounted for by changes in the expression of myosin and myofibrillar proteins isoforms. A proteomic approach has been developed and proved to be a powerful tool to address the complexity of the problem. Major references:
  

Gondin J, Brocca L, Bellinzona E, D'Antona G, Maffiuletti NA, Miotti D, Pellegrino MA & Bottinelli R. (2011). Neuromuscular electrical stimulation training induces atypical adaptations of the human skeletal muscle phenotype: a functional and proteomic analysis. J Appl Physiol 110, 433-450.

Brocca L, Pellegrino MA, Desaphy JF, Pierno S, Camerino DC & Bottinelli R. (2010). Is oxidative stress a cause or consequence of disuse muscle atrophy in mice? A proteomic approach in hindlimb-unloaded mice. Exp Physiol 95, 331-350.

• (VI) the analysis of intracellular signaling pathways which control the adaptations of muscle phenotype, e.g. muscle mass and metabolism, in conditions such as aging, disuse muscle atrophy, steroid and statin administration in humans and mice. A special attention has been put on the role of oxidative stress. Major references:
  

D'Antona G, Mascaro A, Monopoli A, Miglietta D, Ongini E & Bottinelli R. (2013). Nitric oxide prevents atorvastatin-induced skeletal muscle dysfunction and alterations in mice. Muscle Nerve 47, 72-80.

Brocca L, Cannavino J, Coletto L, Biolo G, Sandri M, Bottinelli R & Pellegrino MA. (2012). The time course of the adaptations of human muscle proteome to bed rest and the underlying mechanisms. J Physiol 590, 5211-5230.

Pellegrino MA, Desaphy JF, Brocca L, Pierno S, Camerino DC & Bottinelli R. (2011). Redox homeostasis, oxidative stress and disuse muscle atrophy. The Journal of physiology 589, 2147-2160.

Camerino GM, Pellegrino MA, Brocca L, Digennaro C, Camerino DC, Pierno S & Bottinelli R. (2011). Statin or fibrate chronic treatment modifies the proteomic profile of rat skeletal muscle. Biochemical pharmacology 81, 1054-1064.

Brocca L, Pellegrino MA, Desaphy JF, Pierno S, Camerino DC & Bottinelli R. (2010). Is oxidative stress a cause or consequence of disuse muscle atrophy in mice? A proteomic approach in hindlimb-unloaded mice. Exp Physiol 95, 331-350.

D'Antona G, Pellegrino MA, Carlizzi CN & Bottinelli R. (2007). Deterioration of contractile properties of muscle fibres in elderly subjects is modulated by the level of physical activity. Eur J Appl Physiol 100, 603-611.