АПОПТОЗ И ПАТОЛОГИЯ ПОЧЕК

Обзор дает представление о влиянии некоторых молекулярных механизмов апоптоза на развитие нефропатий различного генеза. Описаны пути реализации и значение молекул апоптоза (р53, PUMA, MDM2, р21) в развитии патологии почек, связанных с повреждением клубочков, ишемией, в развитии почечной недостаточности. Охарактеризован тонкий механизм влияния молекулы р53 на онкогенез. Отмечено, что экспрессия р53 определяет нефротоксичность ряда противоопухолевых препаратов. Функции проапоптотического протеина PUMA определены лишь в контексте онкогенеза и нефротоксичности. Рассмотрена роль молекулы MDM2 как предиктора опухолевой пролиферации и эволюции волчаночного нефрита. Описан существенный вклад белка р21 в развитие острой почечной недостаточности, фокально-сегментарного гломерулосклероза, диабетической нефропатии, а также в прогрессирование аутоиммунных процессов в почках. Апоптоз является активным механизмом в развитии хронической болезни почек, и его дальнейшее изучение определяет возможность поиска инновационных подходов в предупреждении, прогнозировании и лечении болезней почек.

1. Томилина НА, Бикбов БТ. Эпидемиология хронической почечной недостаточности и новые подходы к классификации и оценке тяжести хронических прогрессирующих заболеваний почек. Тер арх 2005; (6): 87-89

2. Смирнов АВ, Добронравов ВА, Каюков ИГ, Есаян АМ. Хроническая болезнь почек: дальнейшее развитие концепции и классификации. Нефрология 2007; (4): 7-17

3. Цаликова ФД. Апоптоз в патогенезе нефропатий. Нефрология и диализ 1999; (3): 127–130

4. Savill J. Apoptosis and the Kidney. J Am Soc Nephrol 1994; (5): 12-21

5. Ярилин АА. Апоптоз: природа феномена и его роль в норме и при патологии. В: Актуальные проблемы патофизиологии. Мороз Б.Б., ред. Медицина, М., 2001;13-56

6. Chang IY, Kim JN, Jun JY et al. Repression of apurinic/ apyrimidinic endonuclease by p53-dependent apoptosis in hydronephrosis-induced rat kidney. Free Radic Res 2011; 45 (6): 728-34

7. Kerr JF, Wyllie AH,Currie AR. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26; 239-257

8. Shankland SJ, Hugo C, Coats SR et al. Changes in cell-cycle protein expression during experimental mesangial proliferative glomerulonephritis. Kidney Int 1996; 50 (4): 1230-9

9. Onel KB, Huo D, Hastings D et al. Lack of association of the TP53 Arg72Pro SNP and the MDM2 SNP309 with systemic lupus erythematosus in Caucasian, African American, and Asian children and adults. Lupus 2009; 18 (1): 61-6

10. Salvador JM, Hollander MC, Nguyen AT et al. Mice lacking the p53-effector gene Gadd45a develop a lupus-like syndrome. Immunity 2002; 16 (4): 499-508

11. Liu J, Yang JR, He YN et al. Accelerated senescence of renal tubular epithelial cells is associated with disease progression of patients with immunoglobulin A (IgA) nephropathy. Transl Res 2012; 159 (6): 454-63

12. Wang JS, Tseng HH, Shih DF et al. Expression of inducible nitric oxide synthase and apoptosis in human lupus nephritis. Nephron 1997; 77 (4): 404-11

13. Cho DS, Joo HJ, Oh DK, Kang JH, Kim YS, Lee KB, Kim SJ. Cyclooxygenase-2 and p53 expression as prognostic indicators in conventional renal cell carcinoma. Yonsei Med J 2005; 46 (1): 133-40

14. Martínez-Salgado C, Rodríguez-Peña AB, López-Novoa JM. Involvement of small RasGTPases and their effectors in chronic renal disease. Cell Mol Life Sci 2008; 65 (3): 477-92

15. Вильгельм АЭ, Заика АИ, Прасолов ВС. Координированное взаимодействие мультифункциональных членов семейства р53 влияет на важнейшие процессы в многоклеточных организмах. Молекулярная биология 2011;45 (1):180-197

16. Чумаков ПМ. Белок р53 и его универсальные функции в многоклеточном организме. Успехи биологической химии 2007; (47): 3-52

17. Govender D, Harilal P, Hadley GP, Chetty R. p53 protein expression in nephroblastomas: a predictor of poor prognosis. Br J Cancer 1998; 77 (2): 314-8

18. Naesens M. Replicative senescence in kidney aging, renal disease, and renal transplantation. Discov Med 2011; 11 (56): 65-75

19. Vousden KH, Prives C. 2009. Blinded by the light: the growing complexity of p53. Cell 137, 413–431

20. Uzzo RG, Rayman P, Kolenko V, et al. Mechanisms of apoptosis in T cells from patients with renal cell carcinoma. Clin Cancer Res 1999; 5 (5): 1219-29

21. Kucab JE, Phillips DH, Arlt VM. Linking environmental carcinogen exposure to TP53 mutations in human tumours using the human TP53 knock-in (Hupki) mouse model. FEBS J 2010; 277 (12): 2567-83

22. Pedersen AE, Stryhn A, Justesen S et al. Wild type p53- specific antibody and T-cell responses in cancer patients. J Immunother 2011 Nov-Dec; 34 (9): 629-40

23. Van den Berg L, Segun AD, Mersch S et al. Regulation of p53 isoform expression in renal cell carcinoma. Front Biosci (Elite Ed) 2010; 2 : 1042-53

24. Warburton HE, Brady M, Vlatković N et al. p53 regulation and function in renal cell carcinoma. Cancer Res 2005; 65 (15): 6498-503

25. Itoi T, Yamana K, Bilim V et al. Impact of frequent Bcl-2 expression on better prognosis in renal cell carcinoma patients. Br J Cancer 2004; 90 (1): 200-5

26. Kuwahara M, Fujisaki N, Kagawa S et al. Determination of p53 protein and high-risk human papillomavirus DNA in carcinomas of the renal pelvis and ureter. Int J Mol Med 1998; 1 (4): 703-7

27. Vaseva AV, Moll UM. The mitochondrial p53 pathway. Biochim Biophys Acta 2009; 1787 (5): 414-20

28. Qiu LQ, Sinniah R, Hsu SI. Coupled induction of iNOS and p53 upregulation in renal resident cells may be linked with apoptotic activity in the pathogenesis of progressive IgA nephropathy. J Am Soc Nephrol 2004; 15 (8): 2066-78

29. Suzuki T, Matsusaka T, Nakayama M et al. Genetic podocyte lineage reveals progressive podocytopenia with parietal cell hyperplasia in a murine model of cellular/collapsing focal segmental glomerulosclerosis. Am J Pathol 2009; 174 (5): 1675-82

30. Mishra PK, Raghuram GV, Panwar H et al. Mitochondrial oxidative stress elicits chromosomal instability after exposure to isocyanates in human kidney epithelial cells. Free Radic Res 2009; 43 (8): 718-28

31. McLaren BK, Zhang PL, Herrera GA. P53 protein is a reliable marker in identification of renal tubular injury. Appl Immunohistochem Mol Morphol 2004; 12 (3): 225-229

32. Dagher PC, Mai EM, Hato T et al. The p53 inhibitor pifithrin-α can stimulate fibrosis in a rat model of ischemic acute kidney injury. Am J Physiol Renal Physiol 2012; 302 (2): F284-91

33. Hochegger K, Koppelstaetter C, Tagwerker A et al. p21 and mTERT are novel markers for determining different ischemic time periods in renal ischemia-reperfusion injury. Am J Physiol Renal Physiol 2007; 292 (2): F762-8

34. Bhatt K, Zhou L, Mi QS et al. MicroRNA-34a is induced via p53 during cisplatin nephrotoxicity and contributes to cell survival. Mol Med 2010; 16 (9-10): 409-16

35. Wang J, Biju MP, Wang MH et al. Cytoprotective effects of hypoxia against cisplatin-induced tubular cell apoptosis: involvement of mitochondrial inhibition and p53 suppression. J Am Soc Nephrol 2006; 17 (7): 1875-85

36. Wei Q, Dong G, Yang T et al. Activation and involvement of p53 in cisplatin-induced nephrotoxicity. Am J Physiol Renal Physiol 2007; 293 (4): F1282-91

37. Jiang M, Wei Q, Wang J et al. Regulation of PUMA-alpha by p53 in cisplatin-induced renal cell apoptosis. Oncogene 2006; 25 (29): 4056-66

38. Kindt N, Menzebach A, Van de Wouwer M et al. Protective role of the inhibitor of apoptosis protein, survivin, in toxin-induced acute renal failure. FASEB J 2008; 22 (2): 510-21

39. Rincon J, Romero M, Viera N et al. Increased oxidative stress and apoptosis in acute puromycinaminonucleoside nephrosis. Int J ExpPathol 2004; 85 (1): 25-33

40. Fujieda M, Morita T, Naruse K et al. Effect of pravastatin on cisplatin-induced nephrotoxicity in rats. Hum Exp Toxicol 2011; 30 (7): 603-15

41. Kim DH, Jung YJ, Lee JE et al. SIRT1 activation by resveratrol ameliorates cisplatin-induced renal injury through deacetylation of p53. Am J Physiol Renal Physiol 2011; 301 (2): F427-35

42. Kume S, Haneda M, Kanasaki K et al. Silent information regulator 2 (SIRT1) attenuates oxidative stress-induced mesangial cell apoptosis via p53 deacetylation. Free Radic Biol Med 2006; 40 (12): 2175-82

43. Shankar S, Singh G, Srivastava RK. Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential. Front Biosci 2007; 12: 4839-54

44. Nelson DA, Tan TT, Rabson AB et al. Hypoxia and defective apoptosis drive genomic instability and tumorigenesis. Genes Dev 2004; 18 (17): 2095-107

45. Noon AP, Vlatković N, Polański R et al. p53 and MDM2 in renal cell carcinoma: biomarkers for disease progression and future therapeutic targets? Cancer 2010; 116 (4): 780-90

46. Haitel A, Wiener HG, Baethge U et al. MDM2 expression as a prognostic indicator in clear cell renal cell carcinoma: comparison with p53 overexpression and clinicopathological parameters. Clin Cancer Res 2000; 6 (5): 1840-4

47. Moch H, Sauter G, Gasser TC et al. p53 protein expression but not mdm-2 protein expression is associated with rapid tumor cell proliferation and prognosis in renal cell carcinoma. Urol Res 1997; 25 Suppl 1 : S25-30

48. Polanski R, Maguire M, Nield PC et al. MDM2 interacts with NME2 (non-metastatic cells 2, protein) and suppresses the ability of NME2 to negatively regulate cell motility. Carcinogenesis 2011; 32 (8): 1133-42

49. Hashimoto H, Sue Y, Saga Y et al. Roles of p53 and MDM2 in tumor proliferation and determination of the prognosis of transitional cell carcinoma of the renal pelvis and ureter. Int J Urol 2000; 7 (12): 457-63

50. Tsao CC, Corn PG. MDM-2 antagonists induce p53- dependent cell cycle arrest but not cell death in renal cancer cell lines. Cancer Biol Ther 2011; 10 (12): 1315-25

51. Allam R, Sayyed S G, Kulkarni OP et al. Mdm2 promotes systemic lupus erythematosus and lupus nephritis. J Am Soc Nephrol 2011; 22 (11): 2016-27

52. Niwa T, Shimizu H. Indoxyl sulfate induces nephrovascular senescence. J Ren Nutr 2012; 22 (1): 102-6

53. Samarakoon R, Overstreet JM, Higgins SP, Higgins PJ. TGF-β1 → SMAD/p53/USF2 → PAI-1 transcriptional axis in ureteral obstruction-induced renal fibrosis. Cell Tissue Res 2012; 347 (1): 117-28

54. Willenbring H, Sharma AD, Vogel A et al. Loss of p21 permits carcinogenesis from chronically damaged liver and kidney epithelial cells despite unchecked apoptosis. Cancer Cell 2008; 14 (1): 59-67

55. Shalitin C, Epelbaum R, Moskovitz B et al. Increased levels of a 21-kDa protein in the circulation of tumor-bearing patients. Cancer Detect Prev 1994; 18 (5): 357-65

56. O’Sullivan GC, Tangney M, Casey G et al. Modulation of p21-activated kinase 1 alters the behavior of renal cell carcinoma. Int J Cancer 2007; 121 (9): 1930-40

57. Whitson JM, Noonan EJ, Pookot D et al. Double strandedRNA-mediated activation of P21 gene induced apoptosis and cell cycle arrest in renal cell carcinoma. Int J Cancer 2009; 125 (2): 446-52

58. Megyesi J, Price PM, Tamayo E et al. The lack of a functional p21(WAF1/CIP1) gene ameliorates progression to chronic renal failure. Proc Natl AcadSci USA 1999; 96 (19): 10830-5

59. Hochegger K, Koppelstaetter-Megyesi J, Udvarhelyi N et al. The p53-independent activation of transcription of p21 WAF1/ CIP1/SDI1 after acute renal failure. Am J Physiol 1996; 271 (6 Pt 2): F1211-6

60. Megyesi J, Andrade L, Vieira JM et al. Positive effect of the induction of p21WAF1/CIP1 on the course of ischemic acute renal failure. Kidney Int 2001; 60 (6): 2164-72

61. Megyesi J, Andrade L, Vieira JM et al. Coordination of the cell cycle is an important determinant of the syndrome of acute renal failure. Am J Physiol Renal Physiol 2002; 283 (4): F810-6

62. Srivastava T, Garola RE, Singh HK. Cell-cycle regulatory proteins in the podocyte in collapsing glomerulopathy in children. Kidney Int 2006; 70 (3): 529-35

63. Balomenos D, Martín-Caballero J, García MI et al. The cell cycle inhibitor p21 controls T-cell proliferation and sex-linked lupus development. Nat Med 2000; 6 (2): 171-6

64. Wolf G. Cell cycle regulation in diabetic nephropathy. Kidney Int Suppl 2000; 77: S59-66

65. Wolf G, Fan YP, Weiss RH. Exogenous attenuation of p21(Waf1/Cip1) decreases mesangial cell hypertrophy as a result of hyperglycemia and IGF-1. J Am Soc Nephrol 2004; 15 (3): 575-84