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Modulation of apoptosis-associated genes bcl-2, bcl-x, and bax during rat liver regeneration.
Cell Growth Differ. 1996 Dec; 7(12):1633-42.CG

Abstract

Liver regeneration (LR) after 70% partial hepatectomy (PH) represents a unique in vivo model of cell cycle and gene regulation. This study was conducted to characterize apoptosis-associated gene expression during LR. The results indicated that transcripts for both bcl-x and bcl-2 exhibited similar patterns of expression during LR with peaks at 6 h post-PH. In contrast, the major 1.1-kb bax transcript exhibited peaks at 18 (P < 0.05) and 72 h (P < 0.001) post-PH. Nuclear run-on analyses for all three genes indicated no detectable transcription rate changes during LR. At 6 h post-PH, when bcl-x mRNA levels were increased by 25-fold (P < 0.001), bcl-x mRNA half-life was elevated 4-fold (P < 0.001). Similarly, bax transcript half-life increased from 2.8 h at 0 h to 4.3 h at 24 h (P < 0.001) and > 8 h at 40 h (P < 0.001) post-PH, coincident with increases in steady-state levels of mRNA. Western blot analyses of Bcl-2 and Bcl-x proteins showed no significant change through 96 h of LR, whereas Bax protein levels cycled in parallel with its mRNA. Interestingly, novel Bax- and Bcl-2-cross-reactive proteins of 31 and 32 kDa, respectively, were detected in nuclei isolated from quiescent liver. When liver growth was induced by the peroxisome proliferator clofibrate, transcript and protein levels were coupled for bcl-x but not for bax. In conclusion, the apoptosis-associated genes bcl-2, bcl-x and bax are modulated at the transcript and protein levels during LR, suggesting a role for these gene products in normal liver growth. The alterations in transcript levels occur posttranscriptionally and involve changes in mRNA stability. Furthermore, unlike bax, steady-state protein and transcript levels are uncoupled for both bcl-2 and bcl-x, suggesting a role for translational regulation during LR after PH.

Authors+Show Affiliations

Department of Medicine, University of Minnesota Medical School, Minneapolis 55455, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8959331

Citation

Kren, B T., et al. "Modulation of Apoptosis-associated Genes Bcl-2, Bcl-x, and Bax During Rat Liver Regeneration." Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research, vol. 7, no. 12, 1996, pp. 1633-42.
Kren BT, Trembley JH, Krajewski S, et al. Modulation of apoptosis-associated genes bcl-2, bcl-x, and bax during rat liver regeneration. Cell Growth Differ. 1996;7(12):1633-42.
Kren, B. T., Trembley, J. H., Krajewski, S., Behrens, T. W., Reed, J. C., & Steer, C. J. (1996). Modulation of apoptosis-associated genes bcl-2, bcl-x, and bax during rat liver regeneration. Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research, 7(12), 1633-42.
Kren BT, et al. Modulation of Apoptosis-associated Genes Bcl-2, Bcl-x, and Bax During Rat Liver Regeneration. Cell Growth Differ. 1996;7(12):1633-42. PubMed PMID: 8959331.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of apoptosis-associated genes bcl-2, bcl-x, and bax during rat liver regeneration. AU - Kren,B T, AU - Trembley,J H, AU - Krajewski,S, AU - Behrens,T W, AU - Reed,J C, AU - Steer,C J, PY - 1996/12/1/pubmed PY - 1996/12/1/medline PY - 1996/12/1/entrez SP - 1633 EP - 42 JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research JO - Cell Growth Differ VL - 7 IS - 12 N2 - Liver regeneration (LR) after 70% partial hepatectomy (PH) represents a unique in vivo model of cell cycle and gene regulation. This study was conducted to characterize apoptosis-associated gene expression during LR. The results indicated that transcripts for both bcl-x and bcl-2 exhibited similar patterns of expression during LR with peaks at 6 h post-PH. In contrast, the major 1.1-kb bax transcript exhibited peaks at 18 (P < 0.05) and 72 h (P < 0.001) post-PH. Nuclear run-on analyses for all three genes indicated no detectable transcription rate changes during LR. At 6 h post-PH, when bcl-x mRNA levels were increased by 25-fold (P < 0.001), bcl-x mRNA half-life was elevated 4-fold (P < 0.001). Similarly, bax transcript half-life increased from 2.8 h at 0 h to 4.3 h at 24 h (P < 0.001) and > 8 h at 40 h (P < 0.001) post-PH, coincident with increases in steady-state levels of mRNA. Western blot analyses of Bcl-2 and Bcl-x proteins showed no significant change through 96 h of LR, whereas Bax protein levels cycled in parallel with its mRNA. Interestingly, novel Bax- and Bcl-2-cross-reactive proteins of 31 and 32 kDa, respectively, were detected in nuclei isolated from quiescent liver. When liver growth was induced by the peroxisome proliferator clofibrate, transcript and protein levels were coupled for bcl-x but not for bax. In conclusion, the apoptosis-associated genes bcl-2, bcl-x and bax are modulated at the transcript and protein levels during LR, suggesting a role for these gene products in normal liver growth. The alterations in transcript levels occur posttranscriptionally and involve changes in mRNA stability. Furthermore, unlike bax, steady-state protein and transcript levels are uncoupled for both bcl-2 and bcl-x, suggesting a role for translational regulation during LR after PH. SN - 1044-9523 UR - https://www.unboundmedicine.com/medline/citation/8959331/Modulation_of_apoptosis_associated_genes_bcl_2_bcl_x_and_bax_during_rat_liver_regeneration_ L2 - http://cgd.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=8959331 DB - PRIME DP - Unbound Medicine ER -