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| Original Paper |
| Dexamethasone inhibits spontaneous apoptosis in primary cultures of human and rat hepatocytes via Bcl-2 and Bcl-xL induction |
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| B Bailly-Maitre1, G de Sousa1, K Boulukos2, J Gugenheim3 and R Rahmani1 |
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1Laboratoire de Pharmaco-Toxicologie Cellulaire et Moléculaire, INRA, 06606 Antibes, France
2Centre de Biochimie, Université de Nice, Faculté des Sciences, 06108 Nice, France
3Laboratoire de Chirurgie Expérimentale-Faculté de Medecine, 06107 Nice Cedex 02, France
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Correspondence to: G de Sousa or R Rahmani, Laboratoire de Pharmaco-Toxicologie Cellulaire et Moléculaire, INRA, 06606, Antibes, France. Tel: 33 4 93 67 88 60; Fax: 33 4 67 30 40; E-mail: rahmani@antibes.inra.fr
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Edited by A Columbano |
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| Abstract |
| We examined the effects of dexamethasone (DEX) on the apoptotic process in primary cultures of human and rat hepatocytes. DEX prolonged cell viability, inhibited the development of an apoptotic morphology, and stabilised the expression of procaspase-3 in both human and rat hepatocytes. In addition, the inhibition of apoptosis by DEX was strongly correlated with a decrease of caspase-3-like protease activity. Moreover, DEX treatment increased the expression of anti-apoptotic Bcl-2 and Bcl-xL proteins in human and rat hepatocytes, respectively, whereas the expression of pro-apoptotic proteins Bcl-xS or Bad was not detected or remained unchanged. The bcl-xL transcript is regulated at the transcriptional level and its expression paralleled that of Bcl-xL protein in DEX-treated rat hepatocytes. Taken together, these results indicate that this glucocorticoid exerts a protective role on cell survival and it delays apoptosis of human and rat hepatocytes by modulating caspase-3-like protease activity and bcl-2 and bcl-x gene expression. Cell Death and Differentiation (2001) 8, 279-288 |
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| Keywords |
| cell death; cultured human and rat hepatocytes; caspase-3; Bcl-2 family |
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| Abbreviations |
| DEX, dexamethasone; FBS, fetal bovine serum; BSA, bovine serum albumin; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; DMSO, dimethyl sulfoxide; TUNEL, TdT-mediated dUTP Nick End Labelling; PBS, phosphate buffer salin; TdT, Terminal deoxynucleotidyl transferase; dUTP, deoxyuridine triphosphates; DEVD-AFC, N-acetyl-Asp-Glu-Val-Asp-aminotrifluoromethylcoumarin; DTT, dichlorodiphenyltrichloroethane; SDS, sodium dodecyl sulphate; NEG, negative-cells, non-treated cells (-); Control-cells, DMSO-treated cells (+), T0, time zero, time of beginning of treatment; Std, Standards |
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| Received 11 October 2000; accepted 9 November 2000 |
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| March 2001, Volume 8, Number 3, Pages 279-288 |
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