Advances in alpha-1-antitrypsin deficiency liver disease

Current Gastroenterology Reports

Volumn 16, Issue 1, 2014, Pages

  Teckman, Jeffrey H ^a   Jain, Ajay ^a  

^a SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Alpha 1 antitrypsin; Apoptosis; Autophagy; Hepatocellular proliferation; Liver

Indexed keywords

4 PHENYLBUTYRIC ACID; ALPHA 1 ANTITRYPSIN; CARBAMAZEPINE; FATTY ACID BINDING PROTEIN; RAPAMYCIN; URSODEOXYCHOLIC ACID;

ALPHA 1 ANTITRYPSIN DEFICIENCY; APOPTOSIS; ARTICLE; DISEASE ASSOCIATION; DRUG MECHANISM; GENE FREQUENCY; HUMAN; LIVER CELL; LIVER CIRRHOSIS; LIVER DISEASE; LIVER INJURY; LIVER REGENERATION; LIVER TRANSPLANTATION; MOLECULAR PATHOLOGY; NONHUMAN; PROTEIN SYNTHESIS; Z GENE; GENETICS; HETEROZYGOTE; HOMOZYGOTE; MUTATION; PATHOLOGY; REVIEW;

ALPHA 1-ANTITRYPSIN; ALPHA 1-ANTITRYPSIN DEFICIENCY; APOPTOSIS; HEPATOCYTES; HETEROZYGOTE; HOMOZYGOTE; HUMANS; LIVER DISEASES; MUTATION;

EID: 84890282331     PISSN: 15228037     EISSN: 1534312X     Source Type: Journal    
DOI: 10.1007/s11894-013-0367-8     Document Type: Article

References (58)

1. Nelson DR, Teckman J, Di Bisceglie AM, Brenner DA. Diagnosis and management of patients with a(1)-antitrypsin (A1AT) deficiency. Clin Gastroenterol Hepatol. 2011. doi:10.1016/j.cgh.2011.12. 028. "White paper" review of a1AT liver disease focused on adult GI practice.
2. Rudnick DA, Liao Y, An JK, Muglia LJ, Perlmutter DH, Teckman JH. Analyses of hepatocellular proliferation in a mouse model of alpha-1-antitrypsin deficiency. Hepatology. 2004;39(4):1048-55. (Pubitemid 38428944)
3. American Thoracic Society/European Respiratory Society Statement. Standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med. 2003;168(7):818-900.
4. Eriksson S. Alpha-1-antitrypsin deficiency: natural course and therapeutic strategies. In: Boyer JL, Blum HE, Maier K-P, Sauerbruch T, Stalder GA, editors. Falk Symposium 115: Liver cirrhosis and its development. Dordrecht: Kluwer Academic Publishers; 2001. p. 307-15.
5. Qu D, Teckman JH, Perlmutter DH. Review: alpha 1-antitrypsin deficiency associated liver disease. J Gastroenterol Hepatol. 1997;12(5):404-16. (Pubitemid 27244506)
6. Lindblad D, Blomenkamp K, Teckman J. Alpha-1-antitrypsin mutant Z protein content in individual hepatocytes correlates with cell death in a mouse model. Hepatology. 2007;46(4):1228-35. doi:10. 1002/hep.21822. (Pubitemid 350144787)
7. Eriksson S. Discovery of alpha 1-antitrypsin deficiency. Lung. 1990;168(Suppl):523-9.
8. Perlmutter DH. Alpha-1-antitrypsin deficiency: diagnosis and treatment. Clin Liver Dis. 2004;8(4):839-59. viii-ix. (Pubitemid 39311146)
9. Sveger T. Liver disease in alpha1-antitrypsin deficiency detected by screening of 200,000 infants. N Engl J Med. 1976;294(24):1316-21.
10. Sveger T. alpha 1-antitrypsin deficiency in early childhood. Pediatrics. 1978;62(1):22-5. (Pubitemid 8371491)
11. Eriksson S. Alpha 1-antitrypsin deficiency. J Hepatol. 1999;30 Suppl 1:34-9.
12. An JK, Blomenkamp K, Lindblad D, Teckman JH. Quantitative isolation of alphalAT mutant Z protein polymers from human and mouse livers and the effect of heat. Hepatology. 2005;41(1):160-7. (Pubitemid 40066394)
13. Sveger T, Eriksson S. The liver in adolescents with alpha 1- antitrypsin deficiency. Hepatology. 1995;22(2):514-7.
14. Cruz PE, Mueller C, Cossette TL, Golant A, Tang Q, Beattie SG, et al. In vivo post-transcriptional gene silencing of alpha-1 antitrypsin by adeno-associated virus vectors expressing siRNA. Lab Investig. 2007;87(9):893-902. doi:10.1038/labinvest. 3700629. (Pubitemid 47267814)
15. Sveger T. The natural history of liver disease in alpha 1-antitrypsin deficient children. Acta Paediatr Scand. 1988;77(6):847-51. (Pubitemid 19008615)
16. Mowat AP. Alpha 1-antitrypsin deficiency (PiZZ): features of liver involvement in childhood. Acta Paediatr Suppl. 1994;393:13-7. (Pubitemid 24152453)
17. Pittschieler K, Massi G. Alpha 1 antitrypsin deficiency in two population groups in north Italy. Padiatr Padol. 1988;23(4):307-11.
18. Eriksson S.A 30-year perspective on alpha 1-antitrypsin deficiency. Chest. 1996;110(6 Suppl):237S-42S.
19. Eriksson S, Lindmark B, Olsson S. Lack of association between hemochromatosis and alpha-antitrypsin deficiency. Acta Med Scand. 1986;219(3):291-4. (Pubitemid 16012365)
20. Pittschieler K. Liver disease and heterozygous alpha-1-antitrypsin deficiency. Acta Paediatr Scand. 1991;80(3):323-7.
21. Kaserbacher R, Propst T, Propst A, Graziadei I, Judmaier G, Vogel W. Association between heterozygous alpha 1-antitrypsin deficiency and genetic hemochromatosis. Hepatology. 1993;18(3):707-8. (Pubitemid 23259972)
22. Propst T, PropstA,Dietze O, JudmaierG, Braunsteiner H, VogelW. High prevalence of viral infection in adults with homozygous and heterozygous alpha 1-antitrypsin deficiency and chronic liver disease. Ann Intern Med. 1992;117(8):641-5.
23. Mahadeva R, Chang WS, Dafforn TR, Oakley DJ, Foreman RC, Calvin J, et al. Heteropolymerization of S, I, and Z alpha1- antitrypsin and liver cirrhosis. J Clin Invest. 1999;103(7):999-1006. (Pubitemid 29169607)
24. Teckman JH, Perlmutter DH. The endoplasmic reticulum degradation pathway for mutant secretory proteins alpha1-antitrypsin Z and S is distinct from that for an unassembled membrane protein. J Biol Chem. 1996;271(22):13215-20. (Pubitemid 26175903)
25. Lomas DA, Elliott PR, Sidhar SK, Foreman RC, Finch JT, Cox DW, et al. alpha 1-Antitrypsin Mmalton (Phe52-deleted) forms loop-sheet polymers in vivo. Evidence for the C sheet mechanism of polymerization. J Biol Chem. 1995;270(28):16864-70.
26. Lomas DA, Finch JT, Seyama K, Nukiwa T, Carrell RW. Alpha 1- antitrypsin Siiyama (Ser53->Phe). Further evidence for intracellular loop-sheet polymerization. J Biol Chem. 1993;268(21):15333-5. (Pubitemid 23222015)
27. Lykavieris P, Ducot B, Lachaux A, Dabadie A, Broue P, Sarles J, et al. Liver disease associated with ZZ alpha1-antitrypsin deficiency and ursodeoxycholic acid therapy in children. J Pediatr Gastroenterol Nutr. 2008;47(5):623-9. doi:10.1097/MPG. 0b013e31817b6dfb.
28. Piitulainen E, Sveger T. Respiratory symptoms and lung function in young adults with severe alpha(1)-antitrypsin deficiency (PiZZ). Thorax. 2002;57(8):705-8. (Pubitemid 34864527)
29. Sveger T, Thelin T, McNeil TF. Young adults with alpha 1- antitrypsin deficiency identified neonatally: their health, knowledge about and adaptation to the high-risk condition. Acta Paediatr. 1997;86(1):37-40. (Pubitemid 27047151)
30. Rudnick DA, Shikapwashya O, Blomenkamp K, Teckman JH. Indomethacin increases liver damage in a murine model of liver injury from alpha-1-antitrypsin deficiency. Hepatology. 2006;44(4):976-82. doi:10.1002/hep.21326. (Pubitemid 46489562)
31. Sveger T, Piitulainen E, Arborelius Jr M. Lung function in adolescents with alpha 1-antitrypsin deficiency. Acta Paediatr. 1994;83(11):1170-3. (Pubitemid 24348087)
32. Eden E,Hammel J, Rouhani FN, BrantlyML, Barker AF, BuistAS, et al. Asthma features in severe alpha1-antitrypsin deficiency: experience of the National Heart, Lung, and Blood Institute Registry. Chest. 2003;123(3):765-71. (Pubitemid 36315491)
33. Hidvegi T, Mirnics K, Hale P, Ewing M, Beckett C, Perlmutter DH. Regulator ofGSignaling 16 is a marker for the distinct endoplasmic reticulum stress state associated with aggregated mutant alpha1- antitrypsin Z in the classical form of alpha1-antitrypsin deficiency. J Biol Chem. 2007;282(38):27769-80. doi:10.1074/jbc. M704330200. (Pubitemid 47529533)
34. James EL, Bottomley SP. The mechanism of alpha 1-antitrypsin polymerization probed by fluorescence spectroscopy. Arch Biochem Biophys. 1998;356(2):296-300. (Pubitemid 28387734)
35. Lomas DA, Evans DL, Finch JT, Carrell RW. The mechanism of Z alpha 1-antitrypsin accumulation in the liver. Nature. 1992;357(6379):605-7.
36. Cabral CM, Choudhury P, Liu Y, Sifers RN. Processing by endoplasmic reticulum mannosidases partitions a secretion-impaired glycoprotein into distinct disposal pathways. J Biol Chem. 2000;275(32):25015-22. (Pubitemid 30626611)
37. Teckman JH, Burrows J, Hidvegi T, Schmidt B, Hale PD, Perlmutter DH. The proteasome participates in degradation of mutant alpha 1- antitrypsin Z in the endoplasmic reticulum of hepatoma-derived hepatocytes. J Biol Chem. 2001;276(48):44865-72.
38. Teckman JH, Perlmutter DH. Retention of mutant alpha(1)- antitrypsin Z in endoplasmic reticulum is associated with an autophagic response. Am J Physiol Gastrointest Liver Physiol. 2000;279(5):G961-74.
39. Sifers RN. Cell biology. Protein degradation unlocked. Science. 2003;299(5611):1330-1. (Pubitemid 36254634)
40. Qu D, Teckman JH, Omura S, Perlmutter DH. Degradation of a mutant secretory protein, alpha1-antitrypsin Z, in the endoplasmic reticulumrequires proteasome activity. J Biol Chem. 1996;271(37): 22791-5. (Pubitemid 26304726)
41. Wu Y, Whitman I, Molmenti E, Moore K, Hippenmeyer P, Perlmutter DH. A lag in intracellular degradation of mutant alpha 1-antitrypsin correlates with the liver disease phenotype in homozygous PiZZ alpha 1-antitrypsin deficiency. ProcNatlAcad SciU S A. 1994;91(19):9014-8.
42. Dafforn TR, Mahadeva R, Elliott PR, Sivasothy P, Lomas DA. A kinetic mechanism for the polymerization of alpha1-antitrypsin. J Biol Chem. 1999;274(14):9548-55.
43. Lomas DA, Mahadeva R. Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy. J Clin Invest. 2002;110(11):1585-90. (Pubitemid 35424233)
44. Wu Y, Swulius MT, Moremen KW, Sifers RN. Elucidation of the molecular logic by which misfolded alpha 1-antitrypsin is preferentially selected for degradation. Proc Natl Acad Sci U S A. 2003;100(14):8229-34. (Pubitemid 36842527)
45. Teckman JH, Gilmore R, Perlmutter DH. Role of ubiquitin in proteasomal degradation of mutant alpha(1)-antitrypsin Z in the endoplasmic reticulum. Am J Physiol Gastrointest Liver Physiol. 2000;278(1):G39-48. (Pubitemid 30108066)
46. Cabral CM, Liu Y, Moremen KW, Sifers RN. Organizational diversity among distinct glycoprotein endoplasmic reticulumassociated degradation programs. Mol Biol Cell. 2002;13(8): 2639-50.
47. Chappell S, Hadzic N, Stockley R, Guetta-Baranes T, Morgan K, Kalsheker N. A polymorphism of the alpha1-antitrypsin gene represents a risk factor for liver disease. Hepatology. 2008;47(1):127-32. doi:10.1002/hep.21979. (Pubitemid 351171049)
48. Pan S, Huang L, McPherson J, Muzny D, Rouhani F, Brantly M, et al. Single nucleotide polymorphism-mediated translational suppression of endoplasmic reticulum mannosidase I modifies the onset of end-stage liver disease in alpha1-antitrypsin deficiency. Hepatology. 2009;50(1):275-81. doi:10.1002/hep.22974.
49. Hidvegi T, Ewing M, Hale P, Dippold C, Beckett C, Kemp C, et al. An autophagy-enhancing drug promotes degradation of mutant alpha1-antitrypsin Z and reduces hepatic fibrosis. Science. 2010;329(5988):229-32. Demonstration that mega doses of carbamazepine in an animal model of a1AT liver disease are associated with increased intrahepatic autophagy and reduced accumulation of a1AT mutant Z protein.
50. Kaushal S, Annamali M, Blomenkamp K, Rudnick D, Halloran D, Brunt EM, et al. Rapamycin reduces intrahepatic alpha-1- antitrypsin mutant Z protein polymers and liver injury in a mouse model. Exp Biol Med (Maywood). 2010;235(6):700-9. In vivo proof of concept that the use of rapamycin to induce increased authphagy in the liver is associated with reduced a1AT mutant Z protein accumulation and reduce liver injury.
51. Lawless MW, Greene CM, Mulgrew A, Taggart CC, O'Neill SJ, McElvaney NG. Activation of endoplasmic reticulum-specific stress responses associated with the conformational disease Z alpha 1-antitrypsin deficiency. J Immunol. 2004;172(9):5722-6. (Pubitemid 38542077)
52. Miller SD, Greene CM, McLean C, Lawless MW, Taggart CC, O'Neill SJ, et al. Tauroursodeoxycholic acid inhibits apoptosis induced by Z alpha-1 antitrypsin via inhibition of Bad. Hepatology. 2007;46(2):496-503. doi:10.1002/hep. 21689. (Pubitemid 47344785)
53. Rudnick DA, Perlmutter DH. Alpha-1-antitrypsin deficiency: a new paradigm for hepatocellular carcinoma in genetic liver disease. Hepatology. 2005;42(3):514-21. (Pubitemid 41233640)
54. Schmidt BZ, Perlmutter DH. Grp78, Grp94, and Grp170 interact with alpha1-antitrypsin mutants that are retained in the endoplasmic reticulum. Am J Physiol Gastrointest Liver Physiol. 2005;289(3): G444-55. (Pubitemid 41216381)
55. Marcus NY, Blomenkamp K, Ahmad M, Teckman JH. Oxidative stress contributes to liver damage in a murine model of alpha-1- antitrypsin deficiency. Exp Biol Med (Maywood). 2012;237(10): 1163-72. doi:10.1258/ebm.2012. 012106. New data documenting oxidative injury resulting from intrahepatic accumulation of a1AT mutant Z protein and the response of the liver.
56. Mueller C, Tang Q, Gruntman A, Blomenkamp K, Teckman J, Song L, et al. Sustained miRNA-mediated knockdown of mutant AAT with simultaneous augmentation of wild-type AAT has minimal effect on global liver miRNA profiles.Mol Ther. 2012. doi:10. 1038/mt.2011.292. This is a new report of a novel and successful, in vivo strategy to treat both the lung and liver disease associated with a1AT deficiency. In the mouse model of a1AT liver disease, mutant Z gene expression can be knocked down, reducing liver damage, while simultaneously inducing synthesis of wild-type a1AT protein to protect the lung from emphysema.
57. Teckman JH. Lack of effect of oral 4-phenylbutyrate on serum alpha-1-antitrypsin in patients with alpha-1-antitrypsin deficiency: a preliminary study. J Pediatr Gastroenterol Nutr. 2004;39(1):34-7.
58. Teckman JH, An JK, Blomenkamp K, Schmidt B, Perlmutter D. Mitochondrial autophagy and injury in the liver in alpha 1- antitrypsin deficiency. Am J Physiol Gastrointest Liver Physiol. 2004;286(5):G851-62. (Pubitemid 38506818)