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Gene Review

ACIN1  -  apoptotic chromatin condensation inducer 1

Homo sapiens

Synonyms: ACINUS, ACN, Acinus, Apoptotic chromatin condensation inducer in the nucleus, KIAA0670, ...
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Disease relevance of ACIN1

  • High-dose corticosteroid therapy is used in various lung diseases, yet it is not known if the drug enters the alveolar acinus [1].
  • The clinical syndrome of liver toxicity (commonly called veno-occlusive disease) that results from cytoreductive therapy before bone marrow transplant is strongly correlated with a constellation of histological lesions involving structures in zone 3 of the liver acinus and the hepatic venules into which sinusoidal blood flows [2].
  • No induction of surface or intracellular HLA class II molecules and of specific mRNA was observed, in all neuroblastomas, with the exception of a nonprototypic cell line, ACN [3].
  • The severity of emphysema, rather than type, appears to be the most important determinant of chronic deterioration of airflow, and in this there may be significant loss of elastic recoil and microscopic emphysema prior to the observed macroscopic destruction of the acinus [4].
  • In contrast, in cases with early nodular regeneration and no significant fibrosis, the activated hepatic stellate cells were distributed throughout the liver parenchyma, involving zones 2 and 3 of the acinus [5].

High impact information on ACIN1

  • The coupling may be widespread (e.g., liver) or confined to one acinus (e.g., salivary gland and pancreas) [6].
  • BACKGROUND & AIMS: Heterogeneity in uridine 5'-diphosphate (UDP) glucuronosyltransferase expression across the human hepatic acinus may be important in the manifestation of certain zone-specific chemical hepatotoxicities [7].
  • Thus, Akt inhibits chromatin condensation during apoptosis by phosphorylating acinus in the nucleus, revealing a specific mechanism by which nuclear Akt promotes cell survival [8].
  • We demonstrate that Akt phosphorylation of acinus on serine 422 and 573 results in its resistance to caspase cleavage in the nucleus and the inhibition of acinus-dependent chromatin condensation [8].
  • Ultrastructural examination of day 7 vector controls revealed acinus-like structures characteristic of normal mammary epithelium [9].

Chemical compound and disease context of ACIN1

  • On Sirius red staining, there was mild fibrosis of the central veins, portal tracts, and terminal portal venules and perisinusoidal fibrosis in zone 1 of the acinus [10].
  • An increased rate of ethanol metabolism is linked to a greater oxygen demand, thus resulting in greater susceptibility to hypoxia in Zone 3 of the liver acinus, a factor which might be responsible for hepatocellular necrosis in alcoholic hepatitis [11].
  • This bicarbonate-homeostatic mechanism operates without threat of hyperammonemia, because a sophisticated structural and functional organisation of ammonia-metabolizing pathways in the liver acinus uncouples urea synthesis from the vital need to eliminate potentially toxic ammonia [12].

Biological context of ACIN1


Anatomical context of ACIN1

  • Differentiation-associated caspase activation involves the release of cytochrome c from the mitochondria and leads to the cleavage of the protein acinus while the poly(ADP-ribose)polymerase remains uncleaved [16].
  • The iNOS was detected in hepatocytes and localized mainly in the periportal zone of the liver acinus [17].
  • Using a three-dimensional basement membrane culture model in which mammary epithelial cells form hollow, acinus-like structures, we previously demonstrated that lumen formation is achieved, in part, through apoptosis of centrally localized cells [18].
  • While Acinus had previously been implicated in apoptosis and was recently identified as a component of the spliceosome, RNPS1 has been described as a general activator of RNA processing [19].
  • To study the role of Acinus for apoptotic nuclear alterations, we generated stable cell lines in which Acinus isoforms were knocked down by inducible and reversible RNA interference [14].

Associations of ACIN1 with chemical compounds

  • The results indicate that the enzymatic capacity to oxidize ethanol is evenly distributed in the acinus and that, after long-term moderate ethanol treatment, despite lack of parenchymal lesions, changes in the activity of enzymes involved in ethanol metabolism are observed.(ABSTRACT TRUNCATED AT 250 WORDS)[20]
  • Conductivity measurements performed in MeOH and 50 and 20% v/v methanol/ACN permitted the evaluation of the associations of the components of the BGE [21].
  • For that purpose, samples and standard solutions were prepared in 25:75 ACN-water media containing 0.3% v/v acetic acid [22].
  • The presence of 1 microM ACN had no effect on the estimated channel opening rate or on the apparent affinity of the receptor for GABA [23].
  • The free solution mobilities of curved and normal 199-bp DNA fragments have been measured in buffer solutions containing various quantities of the organic cosolvents methanol, ethanol, 2-propanol, 2-methyl-2,4-pentanediol (MPD), ethylene glycol, and ACN, using CE [24].

Regulatory relationships of ACIN1

  • The expression of ICAM-1 was enhanced on sinusoidal cells in all zones of the acinus [25].
  • Female rats differ from males, however, in showing a greater hepatic abundance of L-FABP which is expressed almost equally throughout the acinus [26].

Other interactions of ACIN1

  • AQP3 is present on basal cells of both superficial epithelium and gland acinus [27].
  • These studies demonstrated that both CYP1A1 and CYP1A2 messenger RNAs are distributed nonuniformly across the human liver acinus, with levels highest in hepatocytes surrounding terminal hepatic venules and intercalated veins [28].
  • Heterokaryon analysis revealed that SAP18 is a shuttling protein whereas Acinus is restricted to the nucleus [29].
  • Based on studies showing that within the liver acinus, the expression of CYP7A1 is mainly in the pericentral region while HMG-CoA reductase is mainly periportal, we propose that a 'metabolic zonal segregation' plays an important role in coordinate regulation of cholesterol and VLDL metabolism [30].
  • The structure revealed a unique four-helix bundle with a topology of an up-down-extended loop-down-up, a part of which the helix-extended loop-helix represented the SAP (SAF-A/B, Acinus, and PIAS) motif [31].

Analytical, diagnostic and therapeutic context of ACIN1

  • In situ hybridization experiments demonstrated that this increase in IGFBP-1 mRNA was due to a strong expression of IGFBP-1 in the perivenous region 6-12 h after CCl(4) application, extending to the midzonal region of the acinus within 24-48 h [32].
  • Electron microscopy has the resolution required to survey features of MCF-10A cell and acinus architecture that may change with manipulations designed to induce malignant phenotypes [33].
  • PURPOSE: We present a series of 400 patients with tumor in a solitary kidney who underwent open surgical partial nephrectomy performed by a single surgeon (ACN) with a primary focus on postoperative long-term kidney function [34].
  • Chest radiographs and pulmonary function tests show interstitial and restrictive lung disease, while the histologic appearance is that of a centrilobular inflammatory process with small airway fibrosis and inflammation that radiates into the interstitium of the distal acinus in a patchy fashion [35].
  • The perfusion in the periportal zone of an acinus was significantly lower ( 59.0+/-3.3%) than in the pericentral zone (76.2+/-3.1%) [36].


  1. Pulmonary disposition of cortisol. Braude, A.C., Rebuck, A.S. Ann. Intern. Med. (1982) [Pubmed]
  2. Veno-occlusive disease of the liver after marrow transplantation: histological correlates of clinical signs and symptoms. Shulman, H.M., Fisher, L.B., Schoch, H.G., Henne, K.W., McDonald, G.B. Hepatology (1994) [Pubmed]
  3. Different levels of control prevent interferon-gamma-inducible HLA-class II expression in human neuroblastoma cells. Croce, M., De Ambrosis, A., Corrias, M.V., Pistoia, V., Occhino, M., Meazza, R., Giron-Michel, J., Azzarone, B., Accolla, R.S., Ferrini, S. Oncogene (2003) [Pubmed]
  4. Differences and similarities between chronic obstructive pulmonary disease and asthma. Jeffery, P.K. Clin. Exp. Allergy (1999) [Pubmed]
  5. Activation of hepatic stellate cells in liver tissue of patients with fulminant liver failure after treatment with bioartificial liver. Petrovic, L.M., Arkadopoulos, N., Demetriou, A.A. Hum. Pathol. (2001) [Pubmed]
  6. Electrophysiology of mammalian gland cells. Petersen, O.H. Physiol. Rev. (1976) [Pubmed]
  7. Lobular distribution of human liver phenol and bilirubin uridine 5'-diphosphate glucuronosyltransferase messenger RNAs. Chen, F., Zhou, J., Ritter, J.K., Bondy, C.A., Owens, I.S. Gastroenterology (1996) [Pubmed]
  8. Akt phosphorylates acinus and inhibits its proteolytic cleavage, preventing chromatin condensation. Hu, Y., Yao, J., Liu, Z., Liu, X., Fu, H., Ye, K. EMBO J. (2005) [Pubmed]
  9. Suppression of p53 function in normal human mammary epithelial cells increases sensitivity to extracellular matrix-induced apoptosis. Seewaldt, V.L., Mrózek, K., Sigle, R., Dietze, E.C., Heine, K., Hockenbery, D.M., Hobbs, K.B., Caldwell, L.E. J. Cell Biol. (2001) [Pubmed]
  10. Chance discovery of hepatic fibrosis in patient with asymptomatic hypervitaminosis A. Bioulac-Sage, P., Quinton, A., Saric, J., Grimaud, J.A., Mourey, M.S., Balabaud, C. Arch. Pathol. Lab. Med. (1988) [Pubmed]
  11. Hepatocyte demand and substrate supply as factors in the susceptibility to alcoholic liver injury: pathogenesis and prevention. Israel, Y., Orrego, H. Clinics in gastroenterology. (1981) [Pubmed]
  12. Organization of hepatic nitrogen metabolism and its relation to acid-base homeostasis. Häussinger, D. Klin. Wochenschr. (1990) [Pubmed]
  13. Depletion of BRCA1 impairs differentiation but enhances proliferation of mammary epithelial cells. Furuta, S., Jiang, X., Gu, B., Cheng, E., Chen, P.L., Lee, W.H. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  14. Loss of Acinus Inhibits Oligonucleosomal DNA Fragmentation but Not Chromatin Condensation during Apoptosis. Joselin, A.P., Schulze-Osthoff, K., Schwerk, C. J. Biol. Chem. (2006) [Pubmed]
  15. Scanning electron microscope study of the development of the human respiratory acinus. Dilly, S.A. Thorax (1984) [Pubmed]
  16. Specific involvement of caspases in the differentiation of monocytes into macrophages. Sordet, O., Rébé, C., Plenchette, S., Zermati, Y., Hermine, O., Vainchenker, W., Garrido, C., Solary, E., Dubrez-Daloz, L. Blood (2002) [Pubmed]
  17. Distribution of nitric oxide synthase in normal and cirrhotic human liver. McNaughton, L., Puttagunta, L., Martinez-Cuesta, M.A., Kneteman, N., Mayers, I., Moqbel, R., Hamid, Q., Radomski, M.W. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  18. Bim regulation of lumen formation in cultured mammary epithelial acini is targeted by oncogenes. Reginato, M.J., Mills, K.R., Becker, E.B., Lynch, D.K., Bonni, A., Muthuswamy, S.K., Brugge, J.S. Mol. Cell. Biol. (2005) [Pubmed]
  19. ASAP, a novel protein complex involved in RNA processing and apoptosis. Schwerk, C., Prasad, J., Degenhardt, K., Erdjument-Bromage, H., White, E., Tempst, P., Kidd, V.J., Manley, J.L., Lahti, J.M., Reinberg, D. Mol. Cell. Biol. (2003) [Pubmed]
  20. The effect of chronic ethanol ingestion on ethanol metabolizing enzymes in isolated periportal and perivenous rat hepatocytes. Väänänen, H., Salaspuro, M., Lindros, K. Hepatology (1984) [Pubmed]
  21. Ion-pair association and acid-base equilibria in nonaqueous capillary electrophoresis of weakly basic compounds. Carabias-Martínez, R., Rodríguez-Gonzalo, E., Hernández-Méndez, J., Cruz, E.M., Domínguez-Alvarez, J. Electrophoresis (2006) [Pubmed]
  22. Development of a capillary electrophoresis method for the determination of soybean proteins in soybean-rice gluten-free dietary products. García-Ruiz, C., García, M.A., García, M.C., Marina, M.L. Electrophoresis (2006) [Pubmed]
  23. Neuroactive steroids have multiple actions to potentiate GABAA receptors. Akk, G., Bracamontes, J.R., Covey, D.F., Evers, A., Dao, T., Steinbach, J.H. J. Physiol. (Lond.) (2004) [Pubmed]
  24. Effect of organic cosolvents on the free solution mobility of curved and normal DNA molecules. Lu, Y., Stellwagen, E., Stellwagen, N.C. Electrophoresis (2006) [Pubmed]
  25. Expression of cell adhesion molecules, their ligands and tumour necrosis factor alpha in the liver of patients with metastatic gastrointestinal carcinomas. Gulubova, M.V. Histochem. J. (2002) [Pubmed]
  26. Fatty acid-binding protein expression in the liver: its regulation and relationship to the zonation of fatty acid metabolism. Bass, N.M. Mol. Cell. Biochem. (1990) [Pubmed]
  27. Expression and localization of epithelial aquaporins in the adult human lung. Kreda, S.M., Gynn, M.C., Fenstermacher, D.A., Boucher, R.C., Gabriel, S.E. Am. J. Respir. Cell Mol. Biol. (2001) [Pubmed]
  28. Localization of CYP1A1 and CYP1A2 messenger RNA in normal human liver and in hepatocellular carcinoma by in situ hybridization. McKinnon, R.A., Hall, P.D., Quattrochi, L.C., Tukey, R.H., McManus, M.E. Hepatology (1991) [Pubmed]
  29. Biochemical analysis of the EJC reveals two new factors and a stable tetrameric protein core. Tange, T.Ø., Shibuya, T., Jurica, M.S., Moore, M.J. RNA (2005) [Pubmed]
  30. Cholesterol and hepatic lipoprotein assembly and secretion. Kang, S., Davis, R.A. Biochim. Biophys. Acta (2000) [Pubmed]
  31. NMR structure of the N-terminal domain of SUMO ligase PIAS1 and its interaction with tumor suppressor p53 and A/T-rich DNA oligomers. Okubo, S., Hara, F., Tsuchida, Y., Shimotakahara, S., Suzuki, S., Hatanaka, H., Yokoyama, S., Tanaka, H., Yasuda, H., Shindo, H. J. Biol. Chem. (2004) [Pubmed]
  32. Insulin-like growth factor (IGF)-binding protein-1 is highly induced during acute carbon tetrachloride liver injury and potentiates the IGF-I-stimulated activation of rat hepatic stellate cells. Scharf, J.G., Dombrowski, F., Novosyadlyy, R., Eisenbach, C., Demori, I., Kübler, B., Braulke, T. Endocrinology (2004) [Pubmed]
  33. The ultrastructure of MCF-10A acini. Underwood, J.M., Imbalzano, K.M., Weaver, V.M., Fischer, A.H., Imbalzano, A.N., Nickerson, J.A. J. Cell. Physiol. (2006) [Pubmed]
  34. Open partial nephrectomy for tumor in a solitary kidney: experience with 400 cases. Fergany, A.F., Saad, I.R., Woo, L., Novick, A.C. J. Urol. (2006) [Pubmed]
  35. Idiopathic bronchiolocentric interstitial pneumonia. Yousem, S.A., Dacic, S. Mod. Pathol. (2002) [Pubmed]
  36. Intravital microscopic investigation of xenogeneic microcirculation and impact of complement depletion by cobra venom factor. Diefenbeck, M., Linke, R., Seehofer, D., Terajima, H., Thiery, J., Hammer, C. Xenotransplantation (1998) [Pubmed]
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