عملکرد Uncoupling proteinها در بافت‌های مختلف

نوع مقاله : مقاله مروری

نویسندگان

1 دانشیار، گروه زیست‌شناسی، دانشکده‌ی علوم، دانشگاه فردوسی مشهد، مشهد، ایران

2 دانشجوی دکتری، گروه زیست‌شناسی، دانشکده‌ی علوم، دانشگاه فردوسی مشهد، مشهد، ایران

چکیده

مقدمه: یک سلول برای انجام فعالیت‌های خود نیازمند انرژی است. میتوکندری‌ها ماشین تولید انرژی در سلول هستند. UCPs (Uncoupling protein)، پروتئین‌هایی هستند که در غشای داخلی میتوکندری وجود دارند و باعث نشت پروتون از فضای بین دو غشا به ماتریکس میتوکندری می‌شوند. پر واضح است که تغییر در شیب پروتونی موجود در عرض غشای داخلی میتوکندری، تولید (Adenosine triphosphate) ATP را تحت تأثیر قرار می‌دهد. در این مقاله نقش این پروتئین‌ها در بافت‌های مختلف منجمله بافت‌های محیطی و عصبی مرکزی مرور شده است.روش‌ها: مطالعه‌ی کنونی با استفاده از پایگاه‌های اطلاعاتی PubMed، Elsevier، NCBI و EBSCO به بررسی 63 مقاله منتشر‌شده پرداخت تا عملکرد UCPها را در بافت‌های مختلف تشریح کند.یافته‌ها: مطالعات مختلف نشان داده‌اند که UCPها انواع مختلفی دارند و هر نوع از آن‌ها بر اساس بافتی که در آن قرار گرفته‌اند باعث تغییراتی در فعالیت سلول می‌شوند.نتیجه‌گیری: مطالعات در زمینه‌ی نقش این پروتئین‌ها در سیستم عصبی بیشتر به محیط In vitro محدود می‌شود و نیاز به بررسی‌های بیشتر در رابطه با نقش این پروتئین‌ها در شرایط فیزیولوژیک و پاتولوژیک در شرایط In vivo احساس می‌شود. بررسی عملکردهای فیزیولوژیک این پروتئین‌ها می‌تواند راهکارهای جدیدی را برای درمان بیماری‌های نورودژنراتیو بگشاید.

کلیدواژه‌ها


عنوان مقاله [English]

The Function of Uncoupling Proteins in Various Tissues

نویسندگان [English]

  • Masoud Fereidoni 1
  • Zohreh Abbasi 2
1 Associate Professor, Department of Biology, School of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran
2 PhD Student, Department of Biology, School of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran
چکیده [English]

Background: A cell requires energy to do its work. Mitochondria are the energy-producing machines of the cell. Uncoupling proteins (UCPs) located in the inner mitochondrial membrane cause a proton leak from the intermembrane space to the matrix. Clearly, the changes in the proton gradient across the inner membrane affect ATP production. In this paper, the role of these proteins in different tissues as well as peripheral and central nervous tissues has been reviewed.Methods: This study has reviewed 63 publications explaining the various functions of UCPs in different tissues using PubMed, Elsevier, NCBI and EBSCO databases.Findings: Several studies have shown that UCPs, based on the type of tissue, change the cell activity.Conclusion: Studies related to UCPs roles in the nervous system are mostly restricted to the in-vitro situations; thus more investigation seems to be needed to reveal the UCPs actions in the in-vivo conditions of physiologic and pathologic studies. These studies potentially can open some new therapeutic strategies and hopes to cure neurodegenerative diseases.

کلیدواژه‌ها [English]

  • Uncoupling proteins
  • Mitochondria
  • ATP
  • Cell activity
  1. Andrews ZB, Diano S, Horvath TL. Mitochondrial uncoupling proteins in the CNS: in support of function and survival. Nat Rev Neurosci 2005; 6(11): 829-40.
  2. Krauss S, Zhang CY, Lowell BB. The mitochondrial uncoupling-protein homologues. Nat Rev Mol Cell Biol 2005; 6(3): 248-61.
  3. Sluse FE, Jarmuszkiewicz W, Navet R, Douette P, Mathy G, Sluse-Goffart CM. Mitochondrial UCPs: new insights into regulation and impact. Biochim Biophys Acta 2006; 1757(5-6): 480-5.
  4. Fleury C, Sanchis D. The mitochondrial uncoupling protein-2: current status. Int J Biochem Cell Biol 1999; 31(11): 1261-78.
  5. Horvath TL, Diano S, Barnstable C. Mitochondrial uncoupling protein 2 in the central nervous system: neuromodulator and neuroprotector. Biochem Pharmacol 2003; 65(12): 1917-21.
  6. Echtay KS. Mitochondrial uncoupling proteins--what is their physiological role? Free Radic Biol Med 2007; 43(10): 1351-71.
  7. Brand MD, Esteves TC. Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3. Cell Metab 2005; 2(2): 85-93.
  8. Enerback S, Jacobsson A, Simpson EM, Guerra C, Yamashita H, Harper ME, et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 1997; 387(6628): 90-4.
  9. Cannon B, Shabalina IG, Kramarova TV, Petrovic N, Nedergaard J. Uncoupling proteins: a role in protection against reactive oxygen species--or not? Biochim Biophys Acta 2006; 1757(5-6): 449-58.
  10. Fisler JS, Warden CH. Uncoupling proteins, dietary fat and the metabolic syndrome. Nutr Metab (Lond) 2006; 3: 38.
  11. Nedergaard J, Cannon B. The 'novel' 'uncoupling' proteins UCP2 and UCP3: what do they really do? Pros and cons for suggested functions. Exp Physiol 2003; 88(1): 65-84.
  12. Pecqueur C, Alves-Guerra C, Ricquier D, Bouillaud F. UCP2, a metabolic sensor coupling glucose oxidation to mitochondrial metabolism? IUBMB Life 2009; 61(7): 762-7.
  13. Harper ME, Bevilacqua L, Hagopian K, Weindruch R, Ramsey JJ. Ageing, oxidative stress, and mitochondrial uncoupling. Acta Physiol Scand 2004; 182(4): 321-31.
  14. Brand MD. Uncoupling to survive? The role of mitochondrial inefficiency in ageing. Exp Gerontol 2000; 35(6-7): 811-20.
  15. Emre Y, Nubel T. Uncoupling protein UCP2: when mitochondrial activity meets immunity. FEBS Lett 2010; 584(8): 1437-42.
  16. Ricquier D, Bouillaud F. The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochem J 2000; 345 Pt 2: 161-79.
  17. Ricquier D, Miroux B, Cassard-Doulcier AM, Levi-Meyrueis C, Gelly C, Raimbault S, et al. Contribution to the identification and analysis of the mitochondrial uncoupling proteins. J Bioenerg Biomembr 1999; 31(5): 407-18.
  18. Ricquier D, Bouillaud F. Mitochondrial uncoupling proteins: from mitochondria to the regulation of energy balance. J Physiol 2000; 529 Pt 1: 3-10.
  19. Palou A, Pico C, Bonet ML, Oliver P. The uncoupling protein, thermogenin. Int J Biochem Cell Biol 1998; 30(1): 7-11.
  20. Mozo J, Emre Y, Bouillaud F, Ricquier D, Criscuolo F. Thermoregulation: what role for UCPs in mammals and birds? Biosci Rep 2005; 25(3-4): 227-49.
  21. Carroll AM, Haines LR, Pearson TW, Fallon PG, Walsh CM, Brennan CM, et al. Identification of a functioning mitochondrial uncoupling protein 1 in thymus. J Biol Chem 2005; 280(16): 15534-43.
  22. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev 2004; 84(1): 277-359.
  23. Fleury C, Neverova M, Collins S, Raimbault S, Champigny O, Levi-Meyrueis C, et al. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet 1997; 15(3): 269-72.
  24. Diao J, Allister EM, Koshkin V, Lee SC, Bhattacharjee A, Tang C, et al. UCP2 is highly expressed in pancreatic alpha-cells and influences secretion and survival. Proc Natl Acad Sci U S A 2008; 105(33): 12057-62.
  25. Affourtit C, Brand MD. On the role of uncoupling protein-2 in pancreatic beta cells. Biochim Biophys Acta 2008; 1777(7-8): 973-9.
  26. Zhang CY, Baffy G, Perret P, Krauss S, Peroni O, Grujic D, et al. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell 2001; 105(6): 745-55.
  27. Anello M, Lupi R, Spampinato D, Piro S, Masini M, Boggi U, et al. Functional and morphological alterations of mitochondria in pancreatic beta cells from type 2 diabetic patients. Diabetologia 2005; 48(2): 282-9.
  28. Alves-Guerra MC, Rousset S, Pecqueur C, Mallat Z, Blanc J, Tedgui A, et al. Bone marrow transplantation reveals the in vivo expression of the mitochondrial uncoupling protein 2 in immune and nonimmune cells during inflammation. J Biol Chem 2003; 278(43): 42307-12.
  29. Vogler S, Goedde R, Miterski B, Gold R, Kroner A, Koczan D, et al. Association of a common polymorphism in the promoter of UCP2 with susceptibility to multiple sclerosis. J Mol Med (Berl) 2005; 83(10): 806-11.
  30. Teshima Y, Akao M, Jones SP, Marban E. Uncoupling protein-2 overexpression inhibits mitochondrial death pathway in cardiomyocytes. Circ Res 2003; 93(3): 192-200.
  31. Turner JD, Gaspers LD, Wang G, Thomas AP. Uncoupling protein-2 modulates myocardial excitation-contraction coupling. Circ Res 2010; 106(4): 730-8.
  32. Nubel T, Ricquier D. Respiration under control of uncoupling proteins: Clinical perspective. Horm Res 2006; 65(6): 300-10.
  33. Valle A, Oliver J, Roca P. Role of uncoupling proteins in cancer. Cancers 2010; 2(2): 567-91.
  34. Baffy G. Uncoupling protein-2 and cancer. Mitochondrion 2010; 10(3): 243-52.
  35. Derdak Z, Mark NM, Beldi G, Robson SC, Wands JR, Baffy G. The mitochondrial uncoupling protein-2 promotes chemoresistance in cancer cells. Cancer Res 2008; 68(8): 2813-9.
  36. Boss O, Samec S, Paoloni-Giacobino A, Rossier C, Dulloo A, Seydoux J, et al. Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression. FEBS Lett 1997; 408(1): 39-42.
  37. Azzu V, Jastroch M, Divakaruni AS, Brand MD. The regulation and turnover of mitochondrial uncoupling proteins. Biochim Biophys Acta 2010; 1797(6-7): 785-91.
  38. Nabben M, Hoeks J. Mitochondrial uncoupling protein 3 and its role in cardiac- and skeletal muscle metabolism. Physiol Behav 2008; 94(2): 259-69.
  39. Gustafsson H. Uncoupling proteins: regulation by IGF-1 and neuroprotection during hyperglycemia in vitro [PhD Thesis]. Stockholm, Sweden: Department of Neurochemistry and Neurotoxicology, Arrhenius Laboratories for Natural Sciences, Stockholm University; 2004.
  40. Smorodchenko A, Rupprecht A, Sarilova I, Ninnemann O, Brauer AU, Franke K, et al. Comparative analysis of uncoupling protein 4 distribution in various tissues under physiological conditions and during development. Biochim Biophys Acta 2009; 1788(10): 2309-19.
  41. Horvath TL, Warden CH, Hajos M, Lombardi A, Goglia F, Diano S. Brain uncoupling protein 2: uncoupled neuronal mitochondria predict thermal synapses in homeostatic centers. J Neurosci 1999; 19(23): 10417-27.
  42. Richard D, Rivest R, Huang Q, Bouillaud F, Sanchis D, Champigny O, et al. Distribution of the uncoupling protein 2 mRNA in the mouse brain. J Comp Neurol 1998; 397(4): 549-60.
  43. Diano S, Urbanski HF, Horvath B, Bechmann I, Kagiya A, Nemeth G, et al. Mitochondrial uncoupling protein 2 (UCP2) in the nonhuman primate brain and pituitary. Endocrinology 2000; 141(11): 4226-38.
  44. Diano S, Matthews RT, Patrylo P, Yang L, Beal MF, Barnstable CJ, et al. Uncoupling protein 2 prevents neuronal death including that occurring during seizures: a mechanism for preconditioning. Endocrinology 2003; 144(11): 5014-21.
  45. Andrews ZB, Horvath B, Barnstable CJ, Elsworth J, Yang L, Beal MF, et al. Uncoupling protein-2 is critical for nigral dopamine cell survival in a mouse model of Parkinson's disease. J Neurosci 2005; 25(1): 184-91.
  46. Kong D, Vong L, Parton LE, Ye C, Tong Q, Hu X, et al. Glucose stimulation of hypothalamic MCH neurons involves K(ATP) channels, is modulated by UCP2, and regulates peripheral glucose homeostasis. Cell Metab 2010; 12(5): 545-52.
  47. Parton LE, Ye CP, Coppari R, Enriori PJ, Choi B, Zhang CY, et al. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 2007; 449(7159): 228-32.
  48. Dietrich MO, Andrews ZB, Horvath TL. Exercise-induced synaptogenesis in the hippocampus is dependent on UCP2-regulated mitochondrial adaptation. J Neurosci 2008; 28(42): 10766-71.
  49. Deierborg T, Wieloch T, Diano S, Warden CH, Horvath TL, Mattiasson G. Overexpression of UCP2 protects thalamic neurons following global ischemia in the mouse. J Cereb Blood Flow Metab 2008; 28(6): 1186-95.
  50. Andrews ZB, Rivera A, Elsworth JD, Roth RH, Agnati L, Gago B, et al. Uncoupling protein-2 promotes nigrostriatal dopamine neuronal function. Eur J Neurosci 2006; 24(1): 32-6.
  51. Wu Z, Zhao Y, Zhao B. Superoxide anion, uncoupling proteins and Alzheimer's disease. J Clin Biochem Nutr 2010; 46(3): 187-94.
  52. Wu Z, Zhang J, Zhao B. Superoxide anion regulates the mitochondrial free Ca2+ through uncoupling proteins. Antioxid Redox Signal 2009; 11(8): 1805-18.
  53. Haines BA, Mehta SL, Pratt SM, Warden CH, Li PA. Deletion of mitochondrial uncoupling protein-2 increases ischemic brain damage after transient focal ischemia by altering gene expression patterns and enhancing inflammatory cytokines. J Cereb Blood Flow Metab 2010; 30(11): 1825-33.
  54. Mizuno T, Miura-Suzuki T, Yamashita H, Mori N. Distinct regulation of brain mitochondrial carrier protein-1 and uncoupling protein-2 genes in the rat brain during cold exposure and aging. Biochem Biophys Res Commun 2000; 278(3): 691-7.
  55. Horvath B, Spies C, Warden CH, Diano S, Horvath TL. Uncoupling protein 2 in primary pain and temperature afferents of the spinal cord. Brain Res 2002; 955(1-2): 260-3.
  56. Horvath B, Spies C, Horvath G, Kox WJ, Miyamoto S, Barry S, et al. Uncoupling protein 2 (UCP2) lowers alcohol sensitivity and pain threshold. Biochem Pharmacol 2002; 64(3): 369-74.
  57. Mao W, Yu XX, Zhong A, Li W, Brush J, Sherwood SW, et al. UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells. FEBS Lett 1999; 443(3): 326-30.
  58. Adams SH. Uncoupling protein homologs: emerging views of physiological function. J Nutr 2000; 130(4): 711-4.
  59. Liu D, Chan SL, de Souza-Pinto NC, Slevin JR, Wersto RP, Zhan M, et al. Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress. Neuromolecular Med 2006; 8(3): 389-414.
  60. Chu AC, Ho PW, Kwok KH, Ho JW, Chan KH, Liu HF, et al. Mitochondrial UCP4 attenuates MPP+ - and dopamine-induced oxidative stress, mitochondrial depolarization, and ATP deficiency in neurons and is interlinked with UCP2 expression. Free Radic Biol Med 2009; 46(6): 810-20.
  61. Zhang M, Wang B, Ni YH, Liu F, Fei L, Pan XQ, et al. Overexpression of uncoupling protein 4 promotes proliferation and inhibits apoptosis and differentiation of preadipocytes. Life Sci 2006; 79(15): 1428-35.
  62. Sanchis D, Fleury C, Chomiki N, Goubern M, Huang Q, Neverova M, et al. BMCP1, a novel mitochondrial carrier with high expression in the central nervous system of humans and rodents, and respiration uncoupling activity in recombinant yeast. J Biol Chem 1998; 273(51): 34611-5.
  63. Kwok KH, Ho PW, Chu AC, Ho JW, Liu HF, Yiu DC, et al. Mitochondrial UCP5 is neuroprotective by preserving mitochondrial membrane potential, ATP levels, and reducing oxidative stress in MPP+ and dopamine toxicity. Free Radic Biol Med 2010; 49(6): 1023-35.