Tim Parr

Contact

• workRoom B23 North Laboratory
  Sutton Bonington Campus
  Sutton Bonington
  Leicestershire
  LE12 5RD
  UK
• work0115 951 6128
• fax0115 951 6122
• tim.parr@nottingham.ac.uk

Research Summary

Skeletal Muscle Protein Turnover: regulation of proteolysis.

Although skeletal muscle has a primary function of providing locomotion, it is a major depository of protein and free amino acids which are used for gluconeogenesis, wound healing and synthesis of antibodies and acute phase proteins during catabolic diseases. Loss of lean body mass is associated with loss of strength, immune function and with increased disability and mortality. Muscle protein turnover, the balance between protein synthesis and protein breakdown, is effected by various physiological states such as fasting, feeding, disease and aging resulting in a net increase or decrease in protein deposition.

Our research is being carried out into the mechanisms controlling protein degradation, how nutrition modulates this process and how proteolysis by specific enzymes influences metabolism. Our studies have predominantly focused on role of proteolytic enzymes from the calpain family which are believed to be involved in the initiation of muscle protein turnover and have been linked to regulation of carbohydrate oxidation. We are involved in trying to determine the interrelationship between these enzymes and how their activity is regulated, both in the short- and long-term. Changes in these enzymes are being monitored at the gene level, using cDNA and genomic probes, and at the protein level using antibodies. Many of these molecular probes have been generated in-house.

Through the understanding the control of proteolysis tangible benefits could be achieved. In the livestock industry efficiencies in protein gain are constantly being sort and this could be achieved by decreased protein degradation. Also in catabolic conditions, such as in cachexia and sarcopenia, modulation of proteolysis could help to prevent detrimental wasting.

Meat Quality: the role of proteolytic enzyme systems.

The cleavage of specific proteins that maintain the structure of skeletal muscle by proteolytic enzymes is an important factor post-mortem which allows meat to tenderise. Variability in tenderisation process affects meat quality and this has economic consequences for the livestock industry.

The calpain proteolytic system consists of calpain enzyme isoforms and a specific endogenous inhibitor calpastatin. Variation in the ratio of enzyme to inhibitor has been correlated to differences in meat quality; greater toughness being associated with elevated calpastatin activity. We are investigating the role the calpain proteolytic system along with other potential "initiating" proteolytic enzyme systems in the process of meat.

Selected Publications

• KEMP, C. and PARR, T., 2012. Advances in apoptotic mediated proteolysis in meat tenderisation MEAT SCIENCE. 93(3), 252-259
• BROWN DM, PARR T and BRAMELD JM, 2012. Myosin Heavy Chain mRNA Isoforms Are Expressed In Two Distinct Cohorts During C2C12 Myogenesis. Journal Of Muscle Research And Cell Motility. 32(6), 383-390
• STORR, S.J., LEE, K.W., WOOLSTON, C.M., SAFUAN, S., GREEN, A.R., MACMILLAN, R.D., BENHASOUNA, A., PARR, T., ELLIS, I.O. and MARTIN, S.G., 2012. Calpain system protein expression in basal-like and triple-negative invasive breast cancer Annals of Oncology: Official Journal of the European Society for Medical Oncology. 23(9), 2289-2296
• CHAOSAP, C., PARR, T. and WISEMAN, J., 2011. Effect of compensatory growth on forms of glycogen, post mortem proteolysis and meat quality in pigs. Journal of Animal Science. 89(7), 2231-2242

• View all publications

• BREARLEY MC, LI CC, DANIEL ZCTR, LOUGHNA PT, PARR T and BRAMELD JM, 2019. Changes in expression of serine biosynthesis and integrated stress response genes during myogenic differentiation of C2C12 cells Biochemistry and Biophysics Reports. 20, 100694
• BROWN, DAVID, RYAN, KEVIN, DANIEL, ZOE, MAREKO, MOLEBELEDI, TALBOT, RICHARD, MORETON, JOANNA, GILES, TOM C. B., EMES, RICHARD, HODGMAN, CHARLIE, PARR, TIM and BRAMELD, JOHN M., 2019. The Beta-adrenergic agonist, Ractopamine, increases skeletal muscle expression of Asparagine Synthetase as part of an integrated stress response gene program (vol 8, 15915, 2018) SCIENTIFIC REPORTS. 9,
• LOCZENSKI-BROWN, DAVID M., JONES, SARAH, LUCKETT, JENI, DANIEL, ZOE, BREARLEY, MADELAINE C., EBLING, FRANCIS J. P., PARR, TIM and BRAMELD, JOHN M., 2019. Effect of adeno-associated virus (AAV)-mediated overexpression of PEPCK-M ( Pck2) on Clenbuterol-induced muscle growth PLOS ONE. 14(6),
• SLINGER, K. R., STEWART, A. H., DANIEL, Z. C. T. R., HALL, H., O'NEILL, H. V. MASEY, BEDFORD, M. R., PARR, T. and BRAMELD, J. M., 2019. The association between faecal host DNA or faecal calprotectin and feed efficiency in pigs fed yeast-enriched protein concentrate ANIMAL. 13(11), 2483-2491
• MACFADYEN, MHAIRI A., DANIEL, ZOE, KELLY, SARA, PARR, TIM, BRAMELD, JOHN M., MURTON, ANDREW J. and JONES, SIMON W., 2019. The commercial pig as a model of spontaneously-occurring osteoarthritis BMC MUSCULOSKELETAL DISORDERS. 20,
• DALE, TOM N., PARR, TIM, KING, JULIE and BRAMELD, JOHN, 2019. Effects of exogenous fibrolytic enzymes on the release of xylo-oligosaccharides from six varieties of wheat in-vitro JOURNAL OF ANIMAL SCIENCE. 97, 360-361
• BROWN, DAVID M., JONES, SARAH, DANIEL, ZOE C. T. R., BREARLEY, MADELAINE C., LEWIS, JO E., EBLING, FRANCIS J. P., PARR, TIM and BRAMELD, JOHN M., 2018. Effect of sodium 4-phenylbutyrate on Clenbuterol-mediated muscle growth PLOS ONE. 13(7),
• BROWN DM, WILLIAMS H, RYAN KJ, WILSON TL, DANIEL ZC, MAREKO MH, EMES RD, HARRIS DW, JONES S, WATTIS JA, DRYDEN IL, HODGMAN TC, BRAMELD JM and PARR T, 2016. Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth. Scientific reports. 6, 28693
• PARR T, MAREKO MH, RYAN KJ, HEMMINGS KM, BROWN DM and BRAMELD JM, 2016. The impact of growth promoters on muscle growth and the potential consequences for meat quality. Meat science. 120, 93-9
• BRAMELD, JOHN M. and PARR, TIM, 2016. Improving efficiency in meat production PROCEEDINGS OF THE NUTRITION SOCIETY. 75(3), 242-246
• HEMMINGS KM, DANIEL ZCTR, BUTTERY PJ, PARR T and BRAMELD JM, 2015. Differential effects of short-term β agonist and growth hormone treatments on expression of myosin heavy chain IIB and associated metabolic genes in sheep muscle. Animal : an international journal of animal bioscience. 9(2), 285-94
• JING L, HOU Y, WU H, MIAO Y, LI X, CAO J, BRAMELD JM, PARR T and ZHAO S, 2015. Transcriptome analysis of mRNA and miRNA in skeletal muscle indicates an important network for differential Residual Feed Intake in pigs. Scientific reports. 5, 11953
• BROWN DM, BRAMELD JM and PARR T, 2014. Expression of the myosin heavy chain IIB gene in porcine skeletal muscle: the role of the CArG-Box promoter response element. PloS one. 9(12), e114365
• TONGE DP, BARDSLEY RG, PARR T, MACIEWICZ RA and JONES SW, 2014. Evidence of changes to skeletal muscle contractile properties during the initiation of disease in the ageing guinea pig model of osteoarthritis. Longevity & healthspan. 2(1), 15
• RYAN KJ, DANIEL ZC, CRAGGS LJ, PARR T and BRAMELD JM, 2013. Dose-dependent effects of vitamin D on transdifferentiation of skeletal muscle cells to adipose cells. The Journal of endocrinology. 217(1), 45-58
• BROWN DM, PARR T and BRAMELD JM, 2012. Myosin Heavy Chain mRNA Isoforms Are Expressed In Two Distinct Cohorts During C2C12 Myogenesis. Journal Of Muscle Research And Cell Motility. 32(6), 383-390
• STORR, S.J., LEE, K.W., WOOLSTON, C.M., SAFUAN, S., GREEN, A.R., MACMILLAN, R.D., BENHASOUNA, A., PARR, T., ELLIS, I.O. and MARTIN, S.G., 2012. Calpain system protein expression in basal-like and triple-negative invasive breast cancer Annals of Oncology: Official Journal of the European Society for Medical Oncology. 23(9), 2289-2296
• KEMP, C. and PARR, T., 2012. Advances in apoptotic mediated proteolysis in meat tenderisation MEAT SCIENCE. 93(3), 252-259
• STORR, SARAH J, CARRAGHER, NEIL O, FRAME, MARGARET C, PARR, TIM and MARTIN, STEWART G, 2011. The calpain system and cancer. Nature reviews. Cancer. 11(5), 364-74
• GRAHAM, N.S., MAY, S.T., DANIEL, Z.C.T.R., EMMERSON, Z.F., BRAMELD, J.M. and PARR, T., 2011. Use of the Affymetrix Human GeneChip array and genomic DNA hybridisation probe selection to study ovine transcriptomes Animal. 5(6), 861-866
• CHAOSAP, C., PARR, T. and WISEMAN, J., 2011. Effect of compensatory growth on forms of glycogen, post mortem proteolysis and meat quality in pigs. Journal of Animal Science. 89(7), 2231-2242
• STORR, S. J., MOHAMMED, R.A.A., WOOLSTON, C.M., GREEN, A.R., PARR, T., SPITERI, I., CALDAS, C., BALL, G.R., ELLIS, I.O. and MARTIN, S.G., 2011. Calpastatin is associated with lymphovascular invasion in breast cancer The Breast. 20(5), 413-418
• STEPHENS, F.B., NORTON, L., JEWELL, K., CHOKKALINGAM, K., PARR, T. and TSINTZAS, K., 2010. Basal and insulin-stimulated pyruvate dehydrogenase complex activation, glycogen synthesis and metabolic gene expression in human skeletal muscle the day after a single bout of exercise Experimental Physiology. 95(7), 808-818
• ZULKIFLI, R.M., PARR, T., SALTER, A.M. and BRAMELD, J.M., 2010. Regulation of ovine and porcine stearoyl coenzyme A desaturase gene promoters by fatty acids and sterols. Journal of Animal Science. 88(8), 2565-75
• CHAOSAP, C.,, PARR, T. and WISEMAN, J., 2010. Effect of compensatory growth on performance, carcass composition and plasma IGF-1 in grower finisher pigs Animal. 5, 749-756
• TONGE, D.P., JONES, S.W., BARDSLEY, R.G. and PARR, T., 2010. Characterisation of the sarcomeric myosin heavy chain multigene family in the laboratory guinea pig. BMC Molecular Biology. 11, 52
• KEMP CM, SENSKY PL, BARDSLEY RG, BUTTERY PJ and PARR T, 2010. Tenderness--An Enzymatic View. Meat Science. 84(2), 248-56
• TONGE DP, JONES SW, PARR T, BARDSLEY R, DOHERTY M and MACIEWICZ RA, 2010. Beta2-Adrenergic Agonist-Induced Hypertrophy Of The Quadriceps Skeletal Muscle Does Not Modulate Disease Severity In The Rodent Meniscectomy Model Of Osteoarthritis. Osteoarthritis And Cartilage / Oars, Osteoarthritis Research Society. 18(4), 555-62
• HEMMINGS, K.M., PARR, T., DANIEL, Z.C.T.R., PICARD, B., BUTTERY, P.J. and BRAMELD, J.M., 2009. Examination of myosin heavy chain isoform expression in ovine skeletal muscles Journal of Animal Science. 87(12), 3915-3922
• ZÓR K, ORTIZ R, SAATCI E, BARDSLEY R, PARR T, CSÖREGI E and NISTOR M, 2009. Label Free Capacitive Immunosensor For Detecting Calpastatin--A Meat Tenderness Biomarker. Bioelectrochemistry (Amsterdam, Netherlands). 76(1-2), 93-9
• NORTON, L., PARR, T., CHOKKALINGAM, K., BARDSLEY, R.G., YE, H., BELL, G.I., PELSERS, M.M.A.L., VAN LOON, L.J.C. and TSINTZAS, K., 2008. Calpain-10 gene and protein expression in human skeletal muscle: Effect of acute lipid-induced insulin resistance and type 2 diabetes Journal of Clinical Endocrinology and Metabolism. 93(3), 992-998
• SINGH, N, SHRIVASTAV, A, OLSON, D, LAKSHMIKUTTYAMMA, A, ROSS, A, PARR, T and BARDSLEY R. G. & SHARMA R. K., 2008. Cardiac high molecular weight calmodulin-binding protein is homologous to calpastatin I and calpastatin II. Biochemical Biophysical Research Communications. 373, 387-391
• KEMP, C.M and & PARR, T, 2008. The effect of recombinant caspase 3 on myofibrillar proteins in porcine skeletal muscle. Animal. 2, 1254–1264
• FENG, S., SALTER, A.M., PARR, T. and GARNSWORTHY, P.C., 2007. Extraction and quantitative analysis of stearoyl-coenzyme A desaturase mRNA from dairy cow milk somatic cells Journal of Dairy Science. 90(9), 4128-4136
• NORTON, L., PARR, T., BARDSLEY, R. G., YE, H. and TSINTZAS, K., 2007. Characterization of GLUT4 and calpain expression in healthy human skeletal muscle during fasting and refeeding. Acta Physiologica (Oxford, England). 189(3), 233-40
• DE TULLIO, R., AVERNA, M., STIFANESE, R., PARR, T., BARDSLEY, R.G., PONTREMOLI, S. and MELLONI, E., 2007. Multiple rat brain calpastatin forms are produced by distinct starting points and alternative splicing of the N-terminal exons. Archives of Biochemistry and Biophysics. 465(1), 148-56
• KEMP, C.M, SENSKY, P. L, GIBSON S.J, BARDSLEY, R. G and BUTTERY, P.J. & PARR, T., 2007. Fundamental aspects of pig meat science-tenderisation. Paradigms in Pig Science: Proceedings of the 62th University of Nottingham Easter School in Agricultural Science. 395-416
• KEMP, C.M., PARR, T., BARDSLEY, R.G. and BUTTERY, P.J., 2006. Comparison of the relative expression of caspase isoforms in different porcine skeletal muscles Meat Science. 73(3), 426-431
• KEMP, C.M., BARDSLEY, R.G. and PARR, T., 2006. Changes in caspase activity during the postmortem conditioning period and its relationship to shear force in porcine longissimus muscle. Journal of Animal Science. 84(10), 2841-6
• BRAMELD, J., DANIEL, Z., FAHEY, A., PARR, T., SCOLLAN, N. and BUTTERY, P., 2006. Effect of maternal undernutrition on ruminant carcass and meat quality Archiv Für Tierzucht. 49(SPI), 25
• SENSKY, P.L., JEWELL, K.K., RYAN, K.J.P, PARR, T., BARDSLEY, R.G. and BUTTERY, P.J., 2006. Effect of anabolic agents on calpastatin promoters in porcine skeletal muscle and their responsiveness to cyclic adenosine monophosphate- and calcium-related stimuli Journal of Animal Science. 84(11), 2973-82
• MINOBE, ETSUKO, HAO, LI-YING, SAUD, ZAHANGIR A, XU, JIAN-JUN, KAMEYAMA, ASAKO, MAKI, MASATOSHI, JEWELL, KIRSTY K, PARR, TIM, BARDSLEY, RONALD G and KAMEYAMA, MASAKI, 2006. A region of calpastatin domain L that reprimes cardiac L-type Ca2+ channels. Biochemical and biophysical research communications. 348(1), 288-94
• FAHEY, A.J., BRAMELD, J.M., PARR, T. and BUTTERY, P.J., 2005. Ontogeny of factors associated with proliferation and differentiation of muscle in the ovine fetus Journal of Animal Science. 83(10), 2330-2338
• FAHEY, A.J., BRAMELD, J.M., PARR, T. and BUTTERY, P.J., 2005. The effect of maternal undernutrition before muscle differentiation on the muscle fiber development of the newborn lamb Journal of Animal Science. 83(11), 2564-2571
• SAZILI, A.Q., PARR, T., SENSKY, P.L., JONES, S.W., BARDSLEY, R.G. and BUTTERY, P.J., 2005. The relationship between slow and fast myosin heavy chain content, calpastatin and meat tenderness in different ovine skeletal muscles Meat Science. 69(1), 17-25
• RAYNAUD,P., GILLARD,M., PARR,T., BARDSLEY,R.G., AMARGER,V. and LEVEZIEL H., 2005. Correlation between bovine calpastatin mRNA transcripts and protein isoforms Archives of Biochemistry and Biophysics. 440(1), 46-53
• PARR, T., JEWELL, K.K., SENSKY, P.L., BRAMELD, J.M., BARDSLEY, R.G. and BUTTERY, P.J., 2004. Expression of calpastatin isoforms in muscle and functionality of multiple calpastatin promoters Archives of Biochemistry and Biophysics. 427(1), 8-15
• SAZILI, A.Q., LEE, G.K., PARR, T., SENSKY, P.L., BARDSLEY, R.G. and BUTTERY, P.J., 2004. The effect of altered growth rates on the calpain proteolytic system and meat tenderness in cattle Meat Science. 66(1), 195-201
• SENSKY, P.L., BARDSLEY, R.G., BRAMELD, J.M., DANIEL, Z.C., FAHEY, A., JEWELL, K.K., LEE, G.K., PARR, T., SALTER, A.M., SAZILI, A.Q., BUTTERY, P.J., WISEMAN, J., VARLEY, M.A. and KEMP, B., 2003. The biochemical basis for aspects of meat quality. In: WISEMAN, J., VARLEY, M.A. and B. KEMP, eds., Perspectives in pig science Nottingham: Nottingham University Press. 133
• FAHEY, A.J., BRAMELD, J.M., PARR, T. and BUTTERY, P.J., 2003. The effect of reducing protein and energy intake of pregnant ewes on the subsequent muscle development of the offspring. In: SOUFFRANT, W.B. and METGES, C.C., eds., Progress in research on energy and protein metabolism Wageningen: Wageningen Academic Publishers. 151-154
• PARR, T., SENSKY, P.L., BARDSLEY, R.G. and BUTTERY, P.J., 2001. Calpastatin expression in porcine cardiac and skeletal muscle and partial gene structure Archives of Biochemistry and Biophysics. 395(1), 1-13
• PARR, T., SENSKY, P. I., ARNOLD, M. K., BARDSLEY, R. G. and BUTTERY, P. J., 2000. Effects of Epinephrine Infusion on Expression on Calpastatin in Porcine Cardiac and Skeletal Muscle Archives of Biochemistry and Biophysics. VOL 374(PART 2), 299-305
• SENSKY, P.L., PARR, T., SCOTHERN, G.P., BARDSLEY, R.G., BUTTERY, P.J. and WARKUP, C., 1999. The effect of breed on calpastatin isoforms and longissimus shear force in pigmeat In: Proceedings of the British Society of Animal Science 1999. 194
• PARR, T., SENSKY, P.L., WARKUP, C., BARDSLEY, R.G. and BUTTERY, P.J., 1999. Changes in porcine skeletal muscle calpastatin expression induced by a single dose of beta(2) agonist Journal of Animal Science. 77(Supplement 1), 164-165
• SENSKY, P.L., PARR, T., SCOTHERN, G.P., BARDSLEY, R.G., BUTTERY, P.J., WOOD, J.D. and WARKUP, C.C., 1999. Differences in meat quality and the calpain enzyme system in pigs supplied by 4 different commercial production units In: Proceedings of the British Society of Animal Science 1999. 193
• PARR, T., SENSKY, P.L., SCOTHERN, G., BARDSLEY, R.G., BUTTERY, P.J., WOOD, J.D. and WARKUP, C., 1999. Immunochemical study of the calpain system in porcine longissimus muscle with high and low shear force values Journal of Animal Science. 77(Supplement 1), 164
• SENSKY, P.L., PARR, T., LOCKLEY, A.K., BARDSLEY, R.G., BUTTERY, P.J., WOOD, J.D. and WARKUP, C., 1999. Altered calpain levels in longissimus muscle from normal pigs and heterozygotes with the ryanodine receptor mutation Journal of Animal Science. 77(11), 2956-2964
• SCOTHERN, G.P., BUTTERY, P.J., WARKUP, C., BARDSLEY, R.G., WOOD, J.D., PARR, T. and SENSKY, P.L., 1999. Relationship between skeletal muscle-specific calpain and tenderness of conditioned porcine longissimus muscle Journal of Animal Science. 77, 661-668
• JONES, S.W., PARR, T., SENSKY, P.L., SCOTHERN, G.P., BARDSLEY, R.G. and BUTTERY, P.J., 1999. Fibre type-specific expression of p94, a skeletal muscle-specific calpain Journal of Muscle Research and Cell Motility. 20(4), 417-424
• BRAMELD, J.M., SENSKY, P.L., BUDD, T., HARPER, J.M., PARR, T., WARD, R., WRIGHT, M., BARDSLEY, R.G., DAWSON, J., SALTER, A.M. and BUTTERY, P.J., 1998. Protein and fat metabolism in muscle and adipose tissue: its influence on meat quality. In: WISEMAN, J., VARLEY, M.A. and CHADWICK, J.P., eds., Progress in pig science Nottingham: Nottingham University Press. 443-460
• SENSKY, P.L., PARR, T., SCOTHERN, G., PERRY, A., BARDSLEY, R.G., BUTTERY, P.J., WOOD, J.D. and WARKUP, C.C., 1998. Differences in the calpain enzyme system in tough or tender samples of porcine longissimus dorsi In: Proceedings of the British Society of Animal Science 1998. 16
• JONES, S.W., PARR, T., SENSKY, P., BARDSLEY, R.G. and BUTTERY, P.J., 1998. Fibre type-specific expression of the calpain proteolytic system in skeletal muscle Biochemical Society Transactions. 26, S267
• SENSKY, P.L., PARR, T., LOCKLEY, A.K., BARDSLEY, R.G. and BUTTERY, P.J., 1997. Effect of the halothane mutation on the calpain-calpastatin system in porcine longissimus muscle Journal of Animal Science. 75,
• PARR, T., SENSKY, P.L., BUNDICK, Y., BARDSLEY, R.G. and BUTTERY, P.J., 1996. Membrane binding isoforms of calpain inhibitor in heart and skeletal muscle Journal of Muscle Research and Cell Motility. 17, 145-146
• HEISKA, L., KANTOR, C., CRITCHLEY, D.R. and PARR, T., 1996. Binding of the cytoplasmic domain of intercellular adhesion molecule-2 (ICAM-2) to alpha-actinin Journal of Biological Chemistry. 271, 26214-26219
• ARNOLD, M.K., PARR, T., SENSKY, P.L. and BARDSLEY, R.G., 1995. Differential calpastatin expression in cardiac and skeletal muscle Biochemical Society Transactions. 23(3), 454S
• BARDSLEY, R.G., ALLCOCK, S.M., DAWSON, J.M., DUMELOW, N.W., HIGGINS, J.A., LASSLETT, Y.V., LOCKLEY, A.K., PARR, T. and BUTTERY, P.J., 1992. Effect of beta-agonists on expression of calpain and calpastatin activity in skeletal muscle Biochimie. 74, 267-273
• PARR, T., BARDSLEY, R.G., GILMOUR, R.S. and BUTTERY, P.J., 1992. Changes in calpain and calpastatin mRNA induced by beta adrenergic stimulation of bovine skeletal muscle European Journal of Biochemistry. 208, 333-339
• PARR, T., BARDSLEY, R.G., GILMOUR, R.S. and BUTTERY, P.J., 1991. Changes in calpain proteinase mRNA associated with muscle growth stimulated via a-Adrenergic receptors Journal of Muscle Research and Cell Motility. 12, 82
• STORR, S. J., LEE, K. W., WOOLSTON, C. M., SAFUAN, S., GREEN, A. R., MACMILLAN, R. D., BENHASOUNA, A., PARR, T., ELLIS, I. O. and MARTIN, S. G., Calpain system protein expression in basal-like and triple-negative invasive breast cancer ANNALS OF ONCOLOGY. 23(9), 2289-2296