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Gene Review

Bcl2  -  B-cell CLL/lymphoma 2

Rattus norvegicus

Synonyms: Apoptosis regulator Bcl-2, Bcl-2
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Disease relevance of Bcl2

  • Furthermore, we examined the response to hypoxia in an overexpression model of Bcl2 [1].
  • CONCLUSIONS: These findings suggest that chronic CsA nephrotoxicity is related to Bax and Bcl2-related apoptosis pathways, and that alpha-MSH can attenuate the CsA-induced tubulointerstitial fibrosis as well as tubular cell apoptosis [2].
  • Bcl2 expression was not changed by ischemia in any of the animal models [3].
  • An irregular expression of Bcl2 protein was found in untreated and treated lymphomas, while the expression of protein p53 as well as MDM2 was not observed [4].
  • Differential regulation of doxorubicin-induced mitochondrial dysfunction and apoptosis by Bcl-2 in mammary adenocarcinoma (MTLn3) cells [5].

Psychiatry related information on Bcl2


High impact information on Bcl2


Chemical compound and disease context of Bcl2

  • During the treatment, survival of the rats, increase of lymphoma mass, and DNA fragmentation detected by APO/BRDU kit, as well as Bcl2 and p53 protein expression, were followed [13].
  • We have examined these issues in neuron-enriched primary hippocampal cultures, with overexpression of bcl-2 driven by a herpes simplex virus amplicon: (i) Bcl-2 protected strongly against glutamate, whose toxicity is at least partially ROS-dependent [14].
  • C6 glioma cells were stably transfected with a vector expressing Bcl-2 under the control of metallothionin promoter [15].
  • The p53-upregulated modulator of apoptosis (Puma), a BH3-only member of the Bcl-2 protein family, is required for p53-dependent and -independent forms of apoptosis and has been implicated in the pathomechanism of several diseases, including cancer, acquired immunodeficiency syndrome, and ischemic brain disease [16].
  • After exposure to hypoxia for 21 days (10% O2), Bcl-2 protein expression markedly increased, (44%) in gastrocnemius, (323%) in soleus and (1178%) in heart, with significant differences (p < 0.05 student t-test), reaching a similar threshold of expression in both types of muscles [17].

Biological context of Bcl2

  • Neurons also die if deprived of important growth factors and trophic influences, conditions sensitive to certain oncogene products such as the Bcl2 protein [18].
  • Regulation of neuronal Bcl2 protein expression and calcium homeostasis by transforming growth factor type beta confers wide-ranging protection on rat hippocampal neurons [18].
  • Apoptosis of proximal tubule cells was preceded by an increase in the ratio of Bax/Bcl2 proteins, the release of mitochondrial cytochrome c, caspase-3 activation, and DNA fragmentation [19].
  • CONCLUSION: We conclude that changes of quantity and localization of Bcl2 and Bax contribute to hypoxia-mediated apoptosis of GENs in vitro [1].
  • Immunohistochemical analysis in vivo indicated a decrease in cell proliferation (24.68% p < 0.05) and an increase among the TUNEL-positive apoptotic cells along with strong expressions of p53 and Bax, and downregulation of Bcl2 proteins in the mammary tissue of vanadium-treated animals [20].

Anatomical context of Bcl2

  • The expression of Bcl2 mRNA decreased to 0.45- +/- 0.15-fold at 24 hours, whereas that of Bax increased to 7.3- +/- 1.2-fold 1 hour after reoxygenation, accompanied by translocation from the cytosol to mitochondria [1].
  • Thus, progesterone appears to regulate the apoptotic threshold of stromal cells by modulating Bax and Bcl2 expression [21].
  • The purpose of this study was to determine whether regression of the decidua basalis (DB), which begins on Day 14 of pregnancy in the rat, results from an intrinsic program of apoptosis regulated by Bax and Bcl2 [21].
  • Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell [22].
  • Thus, Bcl-2 functions as an inhibitor of mitochondrial permeabilization by changing conformation in the mitochondrial membrane to bind membrane-inserted Bax monomers and prevent productive oligomerization of Bax [23].

Associations of Bcl2 with chemical compounds

  • We now demonstrate that transforming growth factor type beta (TGF-beta) prevents neuronal Ca2+ overloading of rat hippocampal neurons in response to the glutamatergic agonist N-methyl-D-aspartate or the Ca2+ ionophore 4-Br-A23187 and, in addition, leads to a substantial increase in neuronal Bcl2 protein expression [18].
  • Treatment with RU486 on Day 9 enhanced Bax and suppressed Bcl2 within 6 h, increasing the Bax:Bcl2 ratio sixfold (P < 0.05) [21].
  • The current study was undertaken to identify the alterations in mRNA expression for members of the Bcl2-family within the initial hours following ethanol administration on PN4 or PN9 [24].
  • Quantitative real-time PCR studies demonstrated that prolonged palmitic acid supplementation induced down-regulation of the anti-apoptotic Bcl2 mRNA levels (22%) and up-regulation of the pro-apoptotic Bax mRNA levels (300%), leading to disruption of the pro/anti apoptotic balance (Bax/Bcl2=3) [25].
  • When control and Bcl-x(L) cells of equivalent size and pyronin Y fluorescence were compared, the kinetics of cell cycle entry were similar, demonstrating that the ability of Bcl-x(L) and Bcl-2 cells to enhance G(0) arrest contributes significantly to cell cycle delay [26].

Physical interactions of Bcl2

  • If Bax is in excess, apoptosis resumes as Bcl-2 is consumed by the conformational change and in complexes with Bax [23].
  • Insulin-like growth factor-I blocks Bcl-2 interacting mediator of cell death (Bim) induction and intrinsic death signaling in cerebellar granule neurons [27].
  • Recently, it was demonstrated that NGFI-B interacts with Bcl-2 by inducing a conformational change in Bcl-2, converting it from protector to a killer [28].
  • While Gas1 does not directly interact with Bcl-2, OpIAP2 coimmunoprecipitates with Gas1 [29].
  • We propose that the antiapoptotic properties of Bcl-2 are related to the reduction of mitochondrial complex I activity and lowered mitochondrial cytochrome b and c levels [30].

Enzymatic interactions of Bcl2

  • Only a minor fraction of the overexpressed Bcl-2 gets phosphorylated in tamoxifen-treated cells and the phosphorylation does not affect its binding to Bax [15].
  • Finally, an association of Ras and Raf with phosphorylated Bcl-2 protein was demonstrated in immunoprecipitates from apoptotic cells [31].
  • Furthermore, while anti-apoptotic markers, Bcl-2 and phosphorylated Bad, were down-regulated, pro-apoptotic markers, active caspase-3 and Bax, were up-regulated, resulting in the appearance of apoptotic cells in the penile tIssues of OLETF rats [32].

Regulatory relationships of Bcl2


Other interactions of Bcl2

  • The conformationally changed Bcl-2 sequesters the integral membrane form of Bax [23].
  • Identification of Bok as a new pro-apoptotic Bcl-2 protein with restricted tissue distribution and heterodimerization properties could facilitate elucidation of apoptosis mechanisms in reproductive tissues undergoing hormone-regulated cyclic cell turnover [37].
  • Myc-mediated apoptosis is blocked by ectopic expression of Bcl-2 [33].
  • We have now studied the effect of TGF-beta 1 on the expression of different members of the Bcl-2 family in these cells [38].
  • These data suggest a role of dysregulation of Bcl-2 family genes and, at least in atypical lesions, of p53 overexpression, in basal and AMPH-induced apoptosis in nodules and HCCs [39].

Analytical, diagnostic and therapeutic context of Bcl2


  1. Hypoxia-induced apoptosis in cultured glomerular endothelial cells: involvement of mitochondrial pathways. Tanaka, T., Miyata, T., Inagi, R., Kurokawa, K., Adler, S., Fujita, T., Nangaku, M. Kidney Int. (2003) [Pubmed]
  2. The effect of alpha-melanocyte-stimulating hormone on renal tubular cell apoptosis and tubulointerstitial fibrosis in cyclosporine A nephrotoxicity. Lee, S.Y., Jo, S.K., Cho, W.Y., Kim, H.K., Won, N.H. Transplantation (2004) [Pubmed]
  3. Diabetes enhances apoptosis induced by cerebral ischemia. Li, Z.G., Britton, M., Sima, A.A., Dunbar, J.C. Life Sci. (2004) [Pubmed]
  4. Antitumour activity of a combined treatment with PMEDAP and docetaxel in the Prague inbred Sprague-Dawley/cub rat strain bearing T-cell lymphoma. Bobkov, K., Gut, I., Mandys, V., Holý, A., Votruba, I., Otová, B. Anticancer Res. (2001) [Pubmed]
  5. Differential regulation of doxorubicin-induced mitochondrial dysfunction and apoptosis by Bcl-2 in mammary adenocarcinoma (MTLn3) cells. Huigsloot, M., Tijdens, I.B., Mulder, G.J., van de Water, B. J. Biol. Chem. (2002) [Pubmed]
  6. Loss of anti-apoptotic genes in aging rat crura. Yamanaka, M., Shirai, M., Shiina, H., Shirai, M., Tanaka, Y., Fujime, M., Okuyama, A., Dahiya, R. J. Urol. (2002) [Pubmed]
  7. The antiapoptotic actions of mood stabilizers: molecular mechanisms and therapeutic potentials. Chuang, D.M. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  8. Bcl-X(L) inhibits apoptosis and necrosis produced by Alzheimer's beta-amyloid1-40 peptide in PC12 cells. Tan, J., Town, T., Placzek, A., Kundtz, A., Yu, H., Mullan, M. Neurosci. Lett. (1999) [Pubmed]
  9. Differential nigral expression of Bcl-2 protein family in chronically haloperidol and clozapine-treated rats: Role in neurotoxicity and stereotyped behavior. Saldaña, M., Bonastre, M., Aguilar, E., Marin, C. Exp. Neurol. (2007) [Pubmed]
  10. Cell-free apoptosis in Xenopus egg extracts: inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria. Newmeyer, D.D., Farschon, D.M., Reed, J.C. Cell (1994) [Pubmed]
  11. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Shimizu, S., Narita, M., Tsujimoto, Y. Nature (1999) [Pubmed]
  12. Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c. Rossé, T., Olivier, R., Monney, L., Rager, M., Conus, S., Fellay, I., Jansen, B., Borner, C. Nature (1998) [Pubmed]
  13. Anticancer effect of PMEDAP--monitoring of apoptosis. Bobková, K., Otová, B., Marinov, I., Mandys, V., Panczak, A., Votruba, I., Holý, A. Anticancer Res. (2000) [Pubmed]
  14. Neuroprotective effects of bcl-2 overexpression in hippocampal cultures: interactions with pathways of oxidative damage. Howard, S., Bottino, C., Brooke, S., Cheng, E., Giffard, R.G., Sapolsky, R. J. Neurochem. (2002) [Pubmed]
  15. Activated JNK brings about accelerated apoptosis of Bcl-2-overexpressing C6 glioma cells on treatment with tamoxifen. Moodbidri, M.S., Shirsat, N.V. J. Neurochem. (2005) [Pubmed]
  16. Targeted deletion of Puma attenuates cardiomyocyte death and improves cardiac function during ischemia-reperfusion. Toth, A., Jeffers, J.R., Nickson, P., Min, J.Y., Morgan, J.P., Zambetti, G.P., Erhardt, P. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  17. Bcl-2/Bax protein expression in heart, slow-twitch and fast-twitch muscles in young rats growing under chronic hypoxia conditions. Riva, C., Chevrier, C., Pasqual, N., Saks, V., Rossi, A. Mol. Cell. Biochem. (2001) [Pubmed]
  18. Regulation of neuronal Bcl2 protein expression and calcium homeostasis by transforming growth factor type beta confers wide-ranging protection on rat hippocampal neurons. Prehn, J.H., Bindokas, V.P., Marcuccilli, C.J., Krajewski, S., Reed, J.C., Miller, R.J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  19. Activation of pro-apoptotic cascade by dopamine in renal epithelial cells is fully dependent on hydrogen peroxide generation by monoamine oxidases. Bianchi, P., Séguélas, M.H., Parini, A., Cambon, C. J. Am. Soc. Nephrol. (2003) [Pubmed]
  20. Suppression of cell proliferation, induction of apoptosis and cell cycle arrest: Chemopreventive activity of vanadium in vivo and in vitro. Ray, R.S., Ghosh, B., Rana, A., Chatterjee, M. Int. J. Cancer (2007) [Pubmed]
  21. Regression of the decidualized mesometrium and decidual cell apoptosis are associated with a shift in expression of Bcl2 family members. Dai, D., Moulton, B.C., Ogle, T.F. Biol. Reprod. (2000) [Pubmed]
  22. Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell. Leri, A., Claudio, P.P., Li, Q., Wang, X., Reiss, K., Wang, S., Malhotra, A., Kajstura, J., Anversa, P. J. Clin. Invest. (1998) [Pubmed]
  23. Bcl-2 changes conformation to inhibit Bax oligomerization. Dlugosz, P.J., Billen, L.P., Annis, M.G., Zhu, W., Zhang, Z., Lin, J., Leber, B., Andrews, D.W. EMBO J. (2006) [Pubmed]
  24. Altered expression of Bcl2, Bad and Bax mRNA occurs in the rat cerebellum within hours after ethanol exposure on postnatal day 4 but not on postnatal day 9. Ge, Y., Belcher, S.M., Pierce, D.R., Light, K.E. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  25. Palmitate induced lipoapoptosis of exocrine pancreas AR42J cells. Landau, Z., Forti, E., Alcaly, M., Birk, R.Z. Apoptosis (2006) [Pubmed]
  26. Bcl-xL/Bcl-2 coordinately regulates apoptosis, cell cycle arrest and cell cycle entry. Janumyan, Y.M., Sansam, C.G., Chattopadhyay, A., Cheng, N., Soucie, E.L., Penn, L.Z., Andrews, D., Knudson, C.M., Yang, E. EMBO J. (2003) [Pubmed]
  27. Insulin-like growth factor-I blocks Bcl-2 interacting mediator of cell death (Bim) induction and intrinsic death signaling in cerebellar granule neurons. Linseman, D.A., Phelps, R.A., Bouchard, R.J., Le, S.S., Laessig, T.A., McClure, M.L., Heidenreich, K.A. J. Neurosci. (2002) [Pubmed]
  28. ERK2 prohibits apoptosis-induced subcellular translocation of orphan nuclear receptor NGFI-B/TR3. Jacobs, C.M., Boldingh, K.A., Slagsvold, H.H., Thoresen, G.H., Paulsen, R.E. J. Biol. Chem. (2004) [Pubmed]
  29. Gas1 is induced during and participates in excitotoxic neuronal death. Mellström, B., Ceña, V., Lamas, M., Perales, C., Gonzalez, C., Naranjo, J.R. Mol. Cell. Neurosci. (2002) [Pubmed]
  30. Overexpression of bcl-2 results in reduction of cytochrome c content and inhibition of complex I activity. Schwarz, C.S., Evert, B.O., Seyfried, J., Schaupp, M., Kunz, W.S., Vielhaber, S., Klockgether, T., Wüllner, U. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  31. Activated Ha-ras induces apoptosis by association with phosphorylated Bcl-2 in a mitogen-activated protein kinase-independent manner. Navarro, P., Valverde, A.M., Benito, M., Lorenzo, M. J. Biol. Chem. (1999) [Pubmed]
  32. Diminished penile expression of vascular endothelial growth factor and its receptors at the insulin-resistant stage of a type II diabetic rat model: a possible cause for erectile dysfunction in diabetes. Jesmin, S., Sakuma, I., Salah-Eldin, A., Nonomura, K., Hattori, Y., Kitabatake, A. J. Mol. Endocrinol. (2003) [Pubmed]
  33. Myc-mediated apoptosis is blocked by ectopic expression of Bcl-2. Wagner, A.J., Small, M.B., Hay, N. Mol. Cell. Biol. (1993) [Pubmed]
  34. Bcl-2 blocks cisplatin-induced apoptosis by suppression of ERK-mediated p53 accumulation in B104 cells. Park, S.A., Park, H.J., Lee, B.I., Ahn, Y.H., Kim, S.U., Choi, K.S. Brain Res. Mol. Brain Res. (2001) [Pubmed]
  35. Angiotensin type 2 receptor dephosphorylates Bcl-2 by activating mitogen-activated protein kinase phosphatase-1 and induces apoptosis. Horiuchi, M., Hayashida, W., Kambe, T., Yamada, T., Dzau, V.J. J. Biol. Chem. (1997) [Pubmed]
  36. Akt/protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein. Pugazhenthi, S., Nesterova, A., Sable, C., Heidenreich, K.A., Boxer, L.M., Heasley, L.E., Reusch, J.E. J. Biol. Chem. (2000) [Pubmed]
  37. Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-2 family members. Hsu, S.Y., Kaipia, A., McGee, E., Lomeli, M., Hsueh, A.J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  38. Transforming growth factor beta 1 induces apoptosis through cleavage of BAD in a Smad3-dependent mechanism in FaO hepatoma cells. Kim, B.C., Mamura, M., Choi, K.S., Calabretta, B., Kim, S.J. Mol. Cell. Biol. (2002) [Pubmed]
  39. Implication of Bcl-2 family genes in basal and D-amphetamine-induced apoptosis in preneoplastic and neoplastic rat liver lesions. De Miglio, M.R., Muroni, M.R., Simile, M.M., Calvisi, D.F., Tolu, P., Deiana, L., Carru, A., Bonelli, G., Feo, F., Pascale, R.M. Hepatology (2000) [Pubmed]
  40. Bcl-2 overexpression protects against neuron loss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity. Zhao, H., Yenari, M.A., Cheng, D., Sapolsky, R.M., Steinberg, G.K. J. Neurochem. (2003) [Pubmed]
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