İSKELET VE KALP KASLARINDA LAKTİK ASİTİN TAŞINIMI: MONOKARBOKSİL TAŞIYICI PROTEİNLER BÖLÜM I.

Yıl 2005, Cilt: 16 Sayı: 2, 95 - 123, 01.04.2005

Tahir Hazır Caner Açıkada

Öz

Anahtar Kelimeler

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İSKELET VE KALP KASLARINDA LAKTİK ASİTİN TAŞINIMI: MONOKARBOKSİL TAŞIYICI PROTEİNLER BÖLÜM I

Öz

Laktik asit iskelet kasları için hem ana yakıt (oksidatif fibriller) hem de son üründür( glikolitik fibriller). Bu nedenle laktatın plazma membranında taşınımı, onun kasın içine girişi ve çıkışı için önemli bir düzenleyici mekanizmadır. Monokarboksil taşıyıcı proteinler (MCT) laktikasit, pürivik asit ve keton cisimleri gibi monokarboksilli asitleri taşıyan proton bağlantılı taşıyıcı proteinleridir. MCT’ler memelilerde aminoasit içeriğine göre belirlenmiş 14 üyeden oluşan büyük bir taşıyıcı protein ailesidir. Bu proteinlerin bazıları belirli bir dokuya özgünken,diğer bazıları birçok dokuda mevcuttur. İnsan ve sıçanların iskelet ve kalp kaslarında MCT1ve MCT4 olmak üzere iki izoform vardır. Bununla beraber iskelet kaslarında her iki izoformda (MCT1 ve MCT4) mevcutken, sıçanların kalp kasında sadece MCT1 bulunur. MCT1 ilekasın oksidatif fibril kompozisyonu arasında yüksek ilişki vardır. Kasın MCT1 içeriği ile dolaşımdan laktat alımı arasında da yüksek ilişki mevcuttur. MCT4 hızlı kasılan fibrillerle (hızlı glikolitik ve hızlı oksidatif glikolitik) sınırlıdır ve anaerobik metabolizma ile ilişkilidir. Böylece bubilgiler MCT1’in öncelikle dolaşımdan kasa, MCT4’ün ise kasdan dolaşıma laktik asitin taşınımından sorumlu olduğunu gösterir

Anahtar Kelimeler

Laktik asit, Monokarboksil taşıyıcı proteinler, MCT1, MCT4

Kaynakça

• Ahlborg, G., Hagenfeld, L. & Wahren, J. (1975). Substrate utilization by the inactive leg during one-leg or arm exercise. J. Appl. Physiol., 39(5), 718- 723.
• Baker, S.K., McCullagh, K.J.A. & Bonen, A. (1998). Training intensity-dependent and tissue-spesific increases in lacta- te uptake and MCT-1 in heart and muscle. J. Appl. Physiol., 84(3), 987- 994.
• Bangsbo, J., Johansen, L., Graham, T. & Sal- tin, B. (1993). Lactate and H+ efflu- xes from human skeletal muscles du- ring intense, dynamic exercise. J. Physiol., 462, 115-33.
• Benton, C.R., Campbell, S.E., Tonouchi, M., Hatta, H. & Bonen, A. (2004). Mono- carboxylate transporters in subsarco- lemmal and intermyofibrillar mitoc- hondria. Biochem Biophys Res Com- mun., 323(1), 249-53.
• Bonen, A. (2000). Lactate transporters (MCT proteins) in heart and skeletal musc- le. Med. Sci. Sports Exerc., 32 (4), 778-789.
• Bonen, A. (2001). The expression of lactate transporters (MCT1 And MCT4) in he- art and muscle. Eur. J. Appl. Physiol., 86, 6-11.
• Bonen, A., Baker, S.K. & Hatta, H. (1997). Lactate transport and lactate trans- porters in skeletal muscle. Can. J. Appl. Physiol., 22(6), 531-52.
• Bonen, A. & Homonko, D. (1994). Effects of exercise and glycogen depletion on glyconeogenesis in muscle. J.Appl. Physiol., 76, 1753-1758.
• Bonen, A. McDermott, J.C. & Tan, M.H. (1990). Glycogenesis and glycone- ogenesis in skeletal muscle: effects of pH and hormones. Am. J. Physiol., 258 (Endokrinol. Metab. 21), E693- E700.
• Broer, S., Broer, A., Schneider, H-P., Stegen, C. & Halestrap, A.P. (1999). Characte- rization of the high-affinty monocar- boxilate transporter MCT2 in Xeno- pus Laevis oocytes. Biochem. J., 341, 529-535.
• Broer, S., Rahman, B., Pellegri, G., Pellerin, L., Martin, J-L., Verleysdonk, S., Hamprecht, B. & Magistretti, P.J. (1997). Comparition of lactate trans- port in astroglial cells and Monocar- boxylate transporter 1 (MCT1) exprs- sing Xenopus laevis oocytes. Expres- sion of two different monocarboxyla- te transporters in astroglial cells and neurons. 272(48), 30096-30102.
• Broer, S., Schneider, H.P., Broer, A., Rah- man, B., Hamprecht, B. & Deitmer, J.W. (1998). Characterization of the monocarboxylate transporter 1 exp- ressed in Xenopus laevis oocytes by changes in cytosolic pH. Biochem J., 1;333( Pt 1), 167-74.
• Brooks, G.A. (1991). Current concepts in lactate exchange. Med. Sci. Sports Exerc., 23(8), 895-906.
• Brooks, G.A., Brown, M.A., Bunz, C.E., Sıcu- rello, J.P. & Dubouchaud, H. (1999). Cardiac and skeletal muscle mito- condria have a monocarboxylate transporter MCT1. J. Appl. Physiol., 87(5): 1713-1718.
• Carpenter, L. & Halestrap, A.P. (1994). The kinetics, substrate and inhibitor spe- cificity of the lactate transporter of Ehrlich-Lettre tumour cells studied with the intracellular pH indicator BCECF. Biochem J.,15;304 ( Pt 3), 751-60.
• Carpenter, L., Poole, R.C. & Halestrap, A.P. (1996). Cloning and sequencing of the monocarboxylate transporter from mouse Ehrlich Lettre tumour cell confirms its identity as MCT1 and de- monstrates that glycosylation is not required for MCT1 function. Biochim. Biophys. Acta, 1279 (2), 157-163.
• Dimmer, K.S., Friedrich, B., Lang, F., Deit- mer, J.W. & Broer, S. (2000). The low- affinity monocarboxylate transporter MCT4 is adapted to the export of lac- tate in highly glycolytic cells. Bioc- hem J., 15;350 (Pt 1), 219-27.
• Dood, S.L., Powers, S.K., Callender, T. & Brooks, E. (1984). Blood lactate di- sappearance at variouse intensities of recovery exercise. J. Appl. Physi- ol., 57, 1462-1465.
• Edlund, G.L. & Halestrap, A.P. (1988). The ki- netics of transport of lactate and pyruvate into rat hepatocytes. Evi- dence for the presence of a specific carrier similar to that in erythrocytes. Biochem J., 249(1), 117-26.
• Eldridge, F.L. (1975). Relationshipe between turnover and blood concentration in exercise dogs. J. Appl. Physiol., 37, 316-320.
• Fox, J.E.M., Meredith, D. & Halestrap, A.P. (2000). Characterisation of human monocarboxylate transporter 4 subs- tantiates its role in lactic acid efflux from skeletal muscle. J. Physiol., 529(2), 285-293.
• Fishbein, W.N., Merezhinskaya, N. & Foell- mer, J.W. (2002). Relative distribution of three major lactate transporters in frozen human tissues and their locali- zation in unfixed skeletal muscle. Muscle Nerve, 26(1), 101-12.
• Friesema, E.C.H., Ganguly, S., Abdalla, A., Fox, J.E.M., Halestrap, A.P. & Visser, T.J. (2003). Identification of monocar- boxilate transporter 8 as a specific thyroid hormone transporter. J. Biol. Chem., 278(41), 40128-40135.
• Garcia, C.K., Goldstein, J.L., Pathak, R.K., Anderson, R.G. & Brown, M.S. (1994). Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxyla- tes: implications for the Cori cycle. Cell., 76(5), 865-73.
• Garcia, C.K., Li X., Luna, J. & Francke, U. (1994). cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12. Ge- nomics, 23(2), 500-503.
• Garcia, C.K., Brown, M.S., Pathak, R.K. & Goldstein, J.L. (1995). cDNA cloning of MCT2, a second monocarboxylate transporter expressed in different cells than MCT1. J. Biol. Chem., 270 (4), 1843-1849.
• Garcia, C.K., Goldstein, J.L., Pathak, R.K., Anderson, R.G. & Brown, M.S. (1994). Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxyla- tes: implications for the Cori cycle. Cell, 76 (5), 865-873.
• Gerhart, D.Z., Enerson, B.E., Zhdankina, O.Y., Leino, R.L. & Drewes, L.R. (1998). Expression of the monocar- boxylate transporter MCT2 by rat brain glia. Glia, 22 (3), 272-281.
• Gladden, L.B. (1991). Net lactate uptake du- ring progressive steady-level cont- ractions in canin skeletal muscle. J. Appl. Physiol., 71(2), 514-520.
• Gladden, L.B. (2000). Muscle as a consumer of lactate. Med. Sci. Sports Exerc., 32(4), 764-771.
• Gladden, L.B., Crawford, R.E. & Webster, M.J. (1994). Effects of lactate con- centration and metabolic rate on net lactate uptake by canine skeletal muscle. Am, J. Physiol., 266, R1095- R1101.
• Gren, H., Halestrap, A., Mockett, C., O’To- ole, D., Grant, S. & Ouyang , J. (2002). Increases in muscle MCT are associated with reductions in muscle lactate after a single exercise session in humans. Am. J. Physiol. Endocrinol Metab., 282, 154-160.
• Hahn, E.L., Halestrap, A.P. & Gamelli R.L. (2000). Expression of the lactate transporter MCT1 in macrophages. Shock, 13(4), 253-60.
• Halestrap, A.P. & Meredith, D. (2004). The SLC16 gene family-from monocar- boxylate transporters (MCTs) to aro- matic amino acid transporters and beyond. Pflugers Arch., 447(5), 619- 28.
• Higgins, C.F. (1992). ABC transporters: from microorganisms to man. Annu. Rev. Cell Biol., 8: 67-113.
• Hirche, H.H., Langohr, D. & Wacher, U. (1970). Lactic acid permeation from skeletal muscle. Pfluegers Arch., 319, R109.
• Hultman, E. & Spriet, L.L. (1987). Energy me- tabolism and fatigue in working muscle. Donald Macleod, Ron Maug- han, Myra Nimmo, Thomas Relly Clyde Williams (eds). Exercise Bene- fits Limits and Adaptations. (pp 63- 84).London: E. & F.N. Spon Ltd.
• Hughson, R.L., Weisiger, K.H. & Swanson, G.D. (1987) Blood lactate concentra- tion increases as a continuous functi- on in progressive exercise. J. Appl. Physiol., 62(5), 1975-81.
• Jackson, V.N., Price, N.T., Carpenter, L. & Halestrap, A.P. (1997). Cloning of the monocarboxylate transporter isoform MCT2 from rat testis provides evi- dence that expression in tissues is species-specific and may involve post-transcriptional regulation. Bioc- hem. J., 324 (Pt 2), 447-453.
• Jackson, V.N., Price, N.T. & Halestrap, A.P. (1995). cDNA cloning of MCT1, a mo- nocarboxylate transporter from rat skeletal muscle. Biochim. Biophys. Acta, 1238 (2), 193-196.
• Jorfeldt, L., Juhlin-Dannfelt, A. & Karlsson, J. (1978). Lactate release in relation to tissue lactate in human skeletal muscle during exercise. J.Appl. Physiol., 44(3), 350-352.
• Johannsson, E., Nagelhus, E.A., McCullagh, K.J.A., Sejersted O.M., Blackstad T.W., Bonen A. & Ottersen O-P. (1997). Cellular and subcellular exp- ression of the monocarboxylate transporter MCT1 in rat heart. A high resolution immunogold analysis. Circ. Res., 80, 400-407.
• Juel, C. (1997). Lactate-proton cotransport in skeletal muscle. Physiol Rev., 77(2), 321-58.
• Juel, C. & Halestrap, A.P. (1999). Lactate transport in skeletal muscle - role and regulation of the monocarboxylate transporter. J. Physiol.,15;517 (Pt 3), 633-42.
• Juel, C., Holten, M.K. & Dela, F. (2004) . Ef- fects of strength training on muscle lactate release and MCT1 and MCT4 content in healthy and type 2 diabetic humans. J. Physiol. (Lond.), 556 (Pt 1), 297-304.
• Kim, C.M., Goldstein, J.L. & Brown, M.S. (1992). cDNA cloning of MEV, a mu- tant protein that facilitates cellular uptake of mevalonate, and identifica- tion of the point mutation responsib- le for its gain of function. J. Biol. Chem., 267(32), 23113-23121
• Kim, D.K., Kanayi, Y., Chairoungdua, A., Matsuo, H., Cha, S.H. & Endou, H. (2001). Expression cloning of a Na+- independent aromatic amino acid transporter with structural similarity to H+/monocarboxylate transporters. J. Biol. Chem., 276, 17221-17228.
• Kim, D.K., Kanayi, Y., Matsuo, H., Kim, J.Y., Chairoungdua A., Kobayashi Y., Eno- moto A., Cha S.H., Goya T. & Endou H. (2002). The human T-type amino acid transporter-1: characterization, gene organization, and chromosomal location. Genomics 79, 95-103.
• Kobayashi, M. (2004). Fiber type-specific lo- calization of monocarboxylate trans- porters MCT1 and MCT4 in rat skele- tal muscle. Kurume Med. J., 51(3-4), 253-61.
• Koehler-Stec, E.M., Simpson, I.A., Vannucci, S.J., Landschulz, K.T. & Landschulz, W.H. (1998). Monocarboxylate transporter expression in mouse bra- in. Am. J. Physiol., 275(3 Pt 1), E516- E524.
• Lafreniere, R.G., Carrel, L. & Villard, H.F. (1994). A novel transmembrane transporter encoded by the XPCT ge- ne in Xq13.2. Hum.Mol. Genet., 3, 1133-1139.
• Lin, R.Y., Vera, J.C., Chaganti, R.S. & Golde, D.W. (1998). Human monocarboxyla- te transporter 2 (MCT2) is a high affi- nity pyruvate transporter. J. Biol. Chem., 273(44), 28959-28965
• MacRae H.S.-H., Dennis, S.C., Bosch, A.N. & Noakes, T.D. (1992). Effects of tra- ining on lactate production and remo- val during progressive exercise in hu- mans. J.Appl. Physiol., 72, 1649- 1656.
• McCullagh, K.J.A. & Bonen, A. (1995). Redu- ced lactate transport in denervated rat skeletal muscle. Am. J. Physiol. (269) (Regulatory Integrative Comp. Physiol. 38), R884-R888.
• McCullagh, K.J.A., Poole, R.C., Halestrap, A.P., O’brien, M. & Bonen, A. (1997). Chronic electrical stimulation incre- ases MCT-1 and lactate uptake in red and white skeletal muscle. Am. J. Physiol. 271 (Endocrinol.Metab. 36), E239-E246.
• McCullagh, K.J.A., Poole, R.C., Halestrap, A.P., O’brien, M. & Bonen, A. (1996). Role of the lactate transporter (MCT1) in skeletal muscle. Am. J. Physiol. 271 (Endocrinol. Metab. 34), E143- E150.
• McDermott, J.C. & Bonen, A. (1992). Glyco- neogenic and oxidative lactate utili- zation in skeletal muscle. Can. J. Physiol. Pharmacol.,70(1), 142-9.
• Mazzeo, R.S., Brooks, G.A., Schoeller, D.A. & Budinger, T.F. (1986). Disposal of blood (l-13C) lactate in humans du- ring rest and exercise. J.Appl. Physi- ol., 60(1), 232-241.
• Merezhinskaya, N., Fishbein, W.N., Davis, J.I. & Foellmer, J.W. (2000). Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport. Muscle Nevre, 23 (1), 90- 97.
• Merezhinskaya, N., Ogunwuyi, S.A., Mullick, F.G. & Fishbein, W.N. (2004). Presen- ce and localization of three lactic acid transporters (MCT1, -2, and -4) in se- parated human granulocytes, lymphocytes, and monocytes. J. His- tochem. Cytochem., 52(11), 1483-93.
• Orsenigo, M.N., Tosco, M., Bazzini, C., Lafo- renza, U. & Faelli, A. (1999). A mono- carboxylate transporter MCT1 is lo- cated at the basolateral pole of rat je- junum. Exp. Physiol., 84 (6), 1033- 1042.
• Pagliassotti, M.J. & Donovan, C. (1990). Ro- le of cell type in net lactate removal by skeletal muscle. Am, J. Physiol., 258, E635-E642.
• Pellerin, L., Halestrap, A.P. & Pierre, K. (2005). Cellular and subcellular distri- bution of monocarboxylate transpor- ters in cultured brain cells and in the adult brain. J Neurosci Res., 1- 15;79(1-2), 55-64.
• Philp, N.J., Yoon, H. & Grollman, E.F. (1998). Monocarboxylate transporter MCT1 is located in the apical membrane and MCT3 in the basal membrane of rat RPE. Am. J. Physiol., 274 (6 Pt 2), R1824-R1828.
• Philp, N.J., Yoon, H. & Lombardi, L. (2001). Mouse MCT3 gene is expressed pre- ferentially in retinal pigment and cho- roid plexus epithelia. Am. J. Physiol., 280, C1319-C1326.
• Pilegaard, H., Terzis, G., Halestrap, A.P. & Jeul C. (1999). Distribution of the lac- tate/H+ transporter isoforms MCT1 and MCT4 in human skeletal muscle. Am. J. Physiol. Endocrinol. Metab., 276, E843-E848.
• Pilegaard, H., Domino, K., Noland, T., Jeul, C., Hellstein, Y., Halestrap, A.P. & Bangsbo, J. (1999) Effect of high-in- tensity exercise training on lacta- te/H+ transport capacity in human skeletal muscle. Am. J. Physiol. 276 (Endocrinol. Metab. 39), E255-E261.
• Poole, R.C. & Halestrap, A.P. (1992). Identifi- cation and partial purification of the erythrocyte L-lactate transporter. Bi- ochem. J., 283(Pt 3), 855-62.
• Poole, R.C. & Halestrap, A.P. (1993). Trans- port of lactate and other monocar- boxylates across mammalian plasma membranes. Am. J. Physiol. , 264 (4 Pt 1), C761-C782.
• Poole, R.C. & Halestrap, A.P. (1994). N-ter- minal protein sequence analysis of the rabbit erythrocyte lactate trans- porter suggests identity with the clo- ned monocarboxylate transport pro- tein MCT1. Biochem. J., 303 (Pt 3), 755-9.
• Poortsmans, J.R., Bossche, J.V.D. & Lec- lercq, R. (1978). Lactate uptake by inactive forearm during progressive leg exercise. J. Appl. Physiol.: Respi- rat. Environs. Exercise Physiol., 45(6), 835-839.
• Price, N.T., Jackson, V.N. & Halestrap, A.P. (1998). Cloning and sequencing of fo- ur new mammalian monocarboxylate transporter (MCT) homologues con- firms the existence of a transporter family with an ancient past. Bioc- hem. J., 329 (Pt 2), 321-328.
• Rieu, M., Duvallet, A., Scharapan, L., Thieu- lart, L. & Ferry, A. (1988). Blood lac- tate accumulation in intermittent sup- ramaximal exercise. Eur. J. Appl. Physiol. Occup. Physiol., 57(2), 235- 42.
• Roth, D.A. & Brooks, G.A. (1990a). Lactate transport is mediated by a membra- ne-bond carrier in rat skeletal muscle sarkolemmal vesicles. Arch. Bioc- hem. Biophys., 279, 377-385.
• Roth, D.A. & Brooks, G.A. (1990b). Lactate and pyruvate transport is dominated by a gradient-sensitive carrier in rat skeletal muscle sarkolemmal vesic- les. Arch. Biochem. Biophys., 286, 386-394.
• Sahlin, K., Katz,A. & Henriksson ,J. (1987). Redox state and lactate accumulati- on in human skeletal muscle during dynamic exercise. Biochem. J., 245(2), 551-6.
• Sahlin K. (1986). Muscle fatigue and lactic acid accumulation. Acta Physiol Scand Suppl.,556, 83-91.
• Stanley, W.C., Gertz, E.W., Wisneski, J.A., Neese, R.A., Morris, D.L. & Brooks, A.A. (1986). Lactate extraction during net lactate release in legs of humans during exercise. J.Appl. Physiol., 60(4),1116-1120.
• Spriet, L.L., Soderlund, K., Bergstrom, M. & Hultman, E. (1987). Skeletal muscle glycogenolysis, glycolysis, and pH during electrical stimulation in men. J. Appl. Physiol., 62(2), 616-21.
• Takanaga, H., Tamai, I., Inaba, S., Sai, Y., Hi- gashida, H., Yamamoto, H. & Tsuji, A. (1995). cDNA cloning and functional characterization of rat intestinal mo- nocarboxylate transporter. Biochem. Biophys. Res. Commun., 217(1), 370- 377.
• Tamai, I., Takanaga, H., Maeda, H., Sai, Y., Ogihara, T., Higashida, H. & Tsuji, A. (1995). Participation of a proton-cot- ransporter, MCT1, in the intestinal transport of monocarboxylic acids. Biochem Biophys Res Commun., 214(2), 482-9.
• Wilson, M.C., Jackson, V.N., Heddle, C., Pri- ce, N.T., Pilegaard, H., Juel, C., Bo- nen, A., Montgomery,I., Hutter, O.F. & Halestrap, A.P. (1998). Lactic acid eff- lux from white skeletal muscle is ca- talyzed by the monocarboxylate transporter isoform MCT3. J. Biol. Chem., 273(26), 15920-15926.
• Wang, X., Levi, A.J. & Halestrap, A.P. (1994). Kinetics of the sarcolemmal lactate carrier in single heart cells using BCECF to measure pHi. Am. J. Physiol., 267(5 Pt 2), H1759-69.
• Yoon, H., Donoso, L.A. & Philp, N.J. (1999). Cloning of the human monocarboxy- late transporter MCT3 gene: localiza- tion to chromosome 22q12.3-q13.2. Genomics, 60(3), 366-370.
• Yoon, H., Fanelli, A., Grollman,E.F. & Philp, N.J. (1997). Identification of a unique monocarboxylate transporter (MCT3) in retinal pigment epithelium. Bioc- hem. Biophys. Res. Commun., 234 (1), 90-94.