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MeSH Review

In Situ Nick-End Labeling

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Disease relevance of In Situ Nick-End Labeling

  • These data suggesting that anti-IL-12 leads to reversal of colitis by elimination of the Th1 T cells were substantiated by studies showing that anti-IL-12 treatment led to increased numbers of apoptotic cells in the lamina propria and spleen by both TUNEL staining of tissues and dispersed spleen cell populations [1].
  • In tissue sections of CD437-treated MeWo tumors from these animals, apoptotic melanoma cells and c-fos overexpressing cells were colocalized by TdT-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) staining and in situ hybridization [2].
  • In the HT22 hippocampal cell line, we find that toxicity within individual cells induced by polyQ-expanded htt, as revealed by a TUNEL assay, is associated with the localization of the mutant htt within either nuclear or perinuclear aggregates [3].
  • Apoptosis after global ischemia was observed by DNA electrophoresis and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) staining [4].
  • Tumour growth fraction and apoptosis in salivary gland acinic cell carcinomas. Prognostic implications of Ki-67 and bcl-2 expression and of in situ end labelling (TUNEL) [5].

Psychiatry related information on In Situ Nick-End Labeling


High impact information on In Situ Nick-End Labeling

  • Reduction of cps-6 activity caused by a genetic mutation or RNA-mediated interference (RNAi) affects normal DNA degradation, as revealed by increased staining in a TUNEL assay, and results in delayed appearance of cell corpses during development in C. elegans [8].
  • In situ TUNEL staining of tumour sections revealed that DAP kinase expression from the transgene raised the incidence of apoptosis in vivo [9].
  • Genomic DNA replicated in extracts immunodepleted of X-Mre11 complex accumulates DSBs as demonstrated by TUNEL assay and reactivity to phosphorylated histone H2AX antibodies [10].
  • A combination of TUNEL and immunostaining for death-inducing tumor necrosis factor (TNF) family molecules indicated that the apoptotic cells were frequently found in conjugation with TNF-related apoptosis-inducing ligand (TRAIL)-expressing CD3+CD4+ human T cells [11].
  • After fixation, embedding, and sectioning, the growth fraction was quantified by measuring expression of the proliferation marker Ki-67/myb, differentiation was assessed by expression of mucin, and apoptosis was evaluated by the TUNEL assay [12].

Chemical compound and disease context of In Situ Nick-End Labeling


Biological context of In Situ Nick-End Labeling


Anatomical context of In Situ Nick-End Labeling


Associations of In Situ Nick-End Labeling with chemical compounds


Gene context of In Situ Nick-End Labeling

  • Direct evidence for apoptosis was obtained by double staining for terminal deoxynucleotide transferase nick end labeling (TUNEL) and PS-2 expression and by following green fluorescent protein-tagged PS-2 over time [33].
  • Hair cell nuclei showed both apoptotic- and necrotic-like appearances but markers for classic apoptotic pathways (cytochrome c, caspase-9, caspase-3, JNK, TUNEL) were absent [34].
  • Interestingly, TUNEL staining and PCNA staining showed neither enhanced apoptosis nor reduced cell proliferation in the mutant myocardium [35].
  • In the subventricular zone (SVZ) and the granular cell layer (GCL) of the dentate gyrus, harboring neural and other progenitor cells, nitrosylation and p53 peaked 2-12 h after IR, followed by markers for active caspase-3, apoptosis-inducing factor and TUNEL (6-24 h) [36].
  • In patients with a prominent classic vascular pattern, there was no difference of MIB1 labeling index whereas microvessel density and apoptotic index (TUNEL) were significantly higher as compared to all other patients (p<0.05) [37].

Analytical, diagnostic and therapeutic context of In Situ Nick-End Labeling


  1. Anti-interleukin 12 treatment regulates apoptosis of Th1 T cells in experimental colitis in mice. Fuss, I.J., Marth, T., Neurath, M.F., Pearlstein, G.R., Jain, A., Strober, W. Gastroenterology (1999) [Pubmed]
  2. Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis via activation of AP-1 in vitro, and causes growth inhibition in xenografts in vivo. Schadendorf, D., Kern, M.A., Artuc, M., Pahl, H.L., Rosenbach, T., Fichtner, I., Nürnberg, W., Stüting, S., von Stebut, E., Worm, M., Makki, A., Jurgovsky, K., Kolde, G., Henz, B.M. J. Cell Biol. (1996) [Pubmed]
  3. Cell death triggered by polyglutamine-expanded huntingtin in a neuronal cell line is associated with degradation of CREB-binding protein. Jiang, H., Nucifora, F.C., Ross, C.A., DeFranco, D.B. Hum. Mol. Genet. (2003) [Pubmed]
  4. Reduction of apurinic/apyrimidinic endonuclease expression after transient global cerebral ischemia in rats: implication of the failure of DNA repair in neuronal apoptosis. Kawase, M., Fujimura, M., Morita-Fujimura, Y., Chan, P.H. Stroke (1999) [Pubmed]
  5. Tumour growth fraction and apoptosis in salivary gland acinic cell carcinomas. Prognostic implications of Ki-67 and bcl-2 expression and of in situ end labelling (TUNEL). Hellquist, H.B., Sundelin, K., Di Bacco, A., Tytor, M., Manzotti, M., Viale, G. J. Pathol. (1997) [Pubmed]
  6. Evidence for apoptotic cell death in Alzheimer's disease. Smale, G., Nichols, N.R., Brady, D.R., Finch, C.E., Horton, W.E. Exp. Neurol. (1995) [Pubmed]
  7. Overexpression of cyclooxygenase-2 in human HepG2, Bel-7402 and SMMC-7721 hepatoma cell lines and mechanism of cyclooxygenase-2 selective inhibitor celecoxib-induced cell growth inhibition and apoptosis. Liu, N.B., Peng, T., Pan, C., Yao, Y.Y., Shen, B., Leng, J. World J. Gastroenterol. (2005) [Pubmed]
  8. Mitochondrial endonuclease G is important for apoptosis in C. elegans. Parrish, J., Li, L., Klotz, K., Ledwich, D., Wang, X., Xue, D. Nature (2001) [Pubmed]
  9. DAP kinase links the control of apoptosis to metastasis. Inbal, B., Cohen, O., Polak-Charcon, S., Kopolovic, J., Vadai, E., Eisenbach, L., Kimchi, A. Nature (1997) [Pubmed]
  10. Mre11 protein complex prevents double-strand break accumulation during chromosomal DNA replication. Costanzo, V., Robertson, K., Bibikova, M., Kim, E., Grieco, D., Gottesman, M., Carroll, D., Gautier, J. Mol. Cell (2001) [Pubmed]
  11. Critical contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to apoptosis of human CD4+ T cells in HIV-1-infected hu-PBL-NOD-SCID mice. Miura, Y., Misawa, N., Maeda, N., Inagaki, Y., Tanaka, Y., Ito, M., Kayagaki, N., Yamamoto, N., Yagita, H., Mizusawa, H., Koyanagi, Y. J. Exp. Med. (2001) [Pubmed]
  12. Effects of retinoids on cancerous phenotype and apoptosis in organotypic cultures of ovarian carcinoma. Guruswamy, S., Lightfoot, S., Gold, M.A., Hassan, R., Berlin, K.D., Ivey, R.T., Benbrook, D.M. J. Natl. Cancer Inst. (2001) [Pubmed]
  13. Leukotriene B4 receptor antagonist LY293111 inhibits proliferation and induces apoptosis in human pancreatic cancer cells. Tong, W.G., Ding, X.Z., Hennig, R., Witt, R.C., Standop, J., Pour, P.M., Adrian, T.E. Clin. Cancer Res. (2002) [Pubmed]
  14. N-(4-hydroxyphenyl) retinamide is cytotoxic to melanoma cells in vitro through induction of programmed cell death. Montaldo, P.G., Pagnan, G., Pastorino, F., Chiesa, V., Raffaghello, L., Kirchmeier, M., Allen, T.M., Ponzoni, M. Int. J. Cancer (1999) [Pubmed]
  15. Low frequency of apoptosis in Epstein-Barr virus-associated gastric carcinoma with lymphoid stroma. Ohfuji, S., Osaki, M., Tsujitani, S., Ikeguchi, M., Sairenji, T., Ito, H. Int. J. Cancer (1996) [Pubmed]
  16. The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells. Sparrow, J.R., Nakanishi, K., Parish, C.A. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  17. Temporal profile of apoptotic-like changes in neurons and astrocytes following controlled cortical impact injury in the rat. Newcomb, J.K., Zhao, X., Pike, B.R., Hayes, R.L. Exp. Neurol. (1999) [Pubmed]
  18. Flavopiridol, a novel cyclin-dependent kinase inhibitor, suppresses the growth of head and neck squamous cell carcinomas by inducing apoptosis. Patel, V., Senderowicz, A.M., Pinto, D., Igishi, T., Raffeld, M., Quintanilla-Martinez, L., Ensley, J.F., Sausville, E.A., Gutkind, J.S. J. Clin. Invest. (1998) [Pubmed]
  19. Death of smooth muscle cells and expression of mediators of apoptosis by T lymphocytes in human abdominal aortic aneurysms. Henderson, E.L., Geng, Y.J., Sukhova, G.K., Whittemore, A.D., Knox, J., Libby, P. Circulation (1999) [Pubmed]
  20. Tenascin-C is induced with progressive pulmonary vascular disease in rats and is functionally related to increased smooth muscle cell proliferation. Jones, P.L., Rabinovitch, M. Circ. Res. (1996) [Pubmed]
  21. Cripto-1 induces apoptosis in HC-11 mouse mammary epithelial cells. De Santis, M.L., Martinez-Lacaci, I., Bianco, C., Seno, M., Wallace-Jones, B., Kim, N., Ebert, A., Wechselberger, C., Salomon, D.S. Cell Death Differ. (2000) [Pubmed]
  22. Combination treatment with 17-N-allylamino-17-demethoxy geldanamycin and acute irradiation produces supra-additive growth suppression in human prostate carcinoma spheroids. Enmon, R., Yang, W.H., Ballangrud, A.M., Solit, D.B., Heller, G., Rosen, N., Scher, H.I., Sgouros, G. Cancer Res. (2003) [Pubmed]
  23. Fas enhances fibrogenesis in the bile duct ligated mouse: a link between apoptosis and fibrosis. Canbay, A., Higuchi, H., Bronk, S.F., Taniai, M., Sebo, T.J., Gores, G.J. Gastroenterology (2002) [Pubmed]
  24. Effect of ovariectomy on the proliferative capacity of intrahepatic rat cholangiocytes. Alvaro, D., Alpini, G., Onori, P., Franchitto, A., Glaser, S., Le Sage, G., Gigliozzi, A., Vetuschi, A., Morini, S., Attili, A.F., Gaudio, E. Gastroenterology (2002) [Pubmed]
  25. Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. Lucas, J.J., Hernández, F., Gómez-Ramos, P., Morán, M.A., Hen, R., Avila, J. EMBO J. (2001) [Pubmed]
  26. Retinoid-related orphan receptor gamma (RORgamma) is essential for lymphoid organogenesis and controls apoptosis during thymopoiesis. Kurebayashi, S., Ueda, E., Sakaue, M., Patel, D.D., Medvedev, A., Zhang, F., Jetten, A.M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  27. Chronic lymphocytic leukemia B cells are resistant to the apoptotic effects of transforming growth factor-beta. Douglas, R.S., Capocasale, R.J., Lamb, R.J., Nowell, P.C., Moore, J.S. Blood (1997) [Pubmed]
  28. A local action of neurotrophin-3 prevents the death of proliferating sensory neuron precursor cells. ElShamy, W.M., Ernfors, P. Neuron (1996) [Pubmed]
  29. Influence of the nitric oxide donor glyceryl trinitrate on apoptotic pathways in human colon cancer cells. Millet, A., Bettaieb, A., Renaud, F., Prevotat, L., Hammann, A., Solary, E., Mignotte, B., Jeannin, J.F. Gastroenterology (2002) [Pubmed]
  30. Apoptosis induced by environmental stresses and amphotericin B in Candida albicans. Phillips, A.J., Sudbery, I., Ramsdale, M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  31. Mutant cystic fibrosis transmembrane conductance regulator inhibits acidification and apoptosis in C127 cells: possible relevance to cystic fibrosis. Gottlieb, R.A., Dosanjh, A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  32. Role of Rho-associated kinase in neointima formation after vascular injury. Shibata, R., Kai, H., Seki, Y., Kato, S., Morimatsu, M., Kaibuchi, K., Imaizumi, T. Circulation (2001) [Pubmed]
  33. Increased apoptosis arising from increased expression of the Alzheimer's disease-associated presenilin-2 mutation (N141I). Janicki, S., Monteiro, M.J. J. Cell Biol. (1997) [Pubmed]
  34. Caspase-independent pathways of hair cell death induced by kanamycin in vivo. Jiang, H., Sha, S.H., Forge, A., Schacht, J. Cell Death Differ. (2006) [Pubmed]
  35. The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development. Tanaka, M., Chen, Z., Bartunkova, S., Yamasaki, N., Izumo, S. Development (1999) [Pubmed]
  36. Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition. Fukuda, H., Fukuda, A., Zhu, C., Korhonen, L., Swanpalmer, J., Hertzman, S., Leist, M., Lannering, B., Lindholm, D., Björk-Eriksson, T., Marky, I., Blomgren, K. Cell Death Differ. (2004) [Pubmed]
  37. Vascular patterns in glioblastoma influence clinical outcome and associate with variable expression of angiogenic proteins: evidence for distinct angiogenic subtypes. Birner, P., Piribauer, M., Fischer, I., Gatterbauer, B., Marosi, C., Ambros, P.F., Ambros, I.M., Bredel, M., Oberhuber, G., Rössler, K., Budka, H., Harris, A.L., Hainfellner, J.A. Brain Pathol. (2003) [Pubmed]
  38. The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma. Bennett, M.W., O'Connell, J., O'Sullivan, G.C., Brady, C., Roche, D., Collins, J.K., Shanahan, F. J. Immunol. (1998) [Pubmed]
  39. p38 mitogen-activated protein kinase pathway protects adult rat ventricular myocytes against beta -adrenergic receptor-stimulated apoptosis. Evidence for Gi-dependent activation. Communal, C., Colucci, W.S., Singh, K. J. Biol. Chem. (2000) [Pubmed]
  40. Fas (CD95, APO-1) antigen expression and function in murine mast cells. Hartmann, K., Wagelie-Steffen, A.L., von Stebut, E., Metcalfe, D.D. J. Immunol. (1997) [Pubmed]
  41. Transient and reversible deoxyribonucleic acid damage in human left ventricle under controlled ischemia and reperfusion. Corbucci, G.G., Perrino, C., Donato, G., Ricchi, A., Lettieri, B., Troncone, G., Indolfi, C., Chiariello, M., Avvedimento, E.V. J. Am. Coll. Cardiol. (2004) [Pubmed]
  42. TNF-alpha acts to prevent occurrence of malformed fetuses in diabetic mice. Torchinsky, A., Gongadze, M., Orenstein, H., Savion, S., Fein, A., Toder, V. Diabetologia (2004) [Pubmed]
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