FoxO3a mediates transforming growth factor-β1-induced apoptosis in FaO rat hepatoma cells

被引：10

作者：

Kim, Byung-Chul ^{[1
]}

机构：

[1] Kangwon Natl Univ, Coll Nat Sci, Dept Biochem, Chunchon 200701, South Korea

来源：

BMB REPORTS | 2008年 / 41卷 / 10期

关键词：

Akt; Apoptosis; FoxO3a; Hepatoma cells; TGF-beta; 1;

D O I：

10.5483/BMBRep.2008.41.10.728

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

FoxO3a is a member of the forkhead box class O (FoxO) transcription factor family and an important regulator of apoptosis. This work aimed to elucidate the involvement of FoxO3a in transforming growth factor-beta 1 (TGF-beta 1)-induced apoptosis in FaO rat hepatoma cells. TGF-beta 1 caused a time-dependent activation of FoxO3a and a subsequent increase in FoxO response-element-containing luciferase reporter activity, which was Akt-sensitive. The FaO cells stably transfected with a wild type FoxO3a were more susceptible to the formation of apoptotic bodies, populations of sub-G1 apoptotic cells, and collapse of the mitochondrial-membrane potential triggered by TGF-beta 1. In contrast, transfection with small-interfering RNA (siRNA) oligonucleotide specific for FoxO3a significantly inhibited caspase activation in FaO cells treated with TGF-beta 1. It thus appears that FoxO3a plays a crucial mediatory role in the TGF-beta 1 signaling pathway leading to apoptosis. [BMB reports 2008; 41(10): 728-732]

引用

页码：728 / 732

页数：5

共 25 条

[1] FoxOs at the crossroads of cellular metabolism, differentiation, and transformation [J].

Accili, D ;

Arden, KC .

CELL, 2004, 117 (04) :421-426

[2] Transcriptional regulation of Bim by FoxO3A mediates hepatocyte lipoapoptosis [J].

Barreyro, Fernando J. ;

Kobayashi, Shogo ;

Bronk, Steven F. ;

Werneburg, Nathan W. ;

Malhi, Harmeet ;

Gores, Gregory J. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (37) :27141-27154

[3] Transforming growth factor beta mediates hepatocyte apoptosis through Smad3 generation of reactive oxygen species [J].

Black, Dalliah ;

Lyman, Suzanne ;

Qian, Ting ;

Lemasters, John J. ;

Rippe, Richard A. ;

Nitta, Takashi ;

Kim, Jae-Sung ;

Behrns, Kevin E. .

BIOCHIMIE, 2007, 89 (12) :1464-1473

[4] Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor [J].

Brunet, A ;

Bonni, A ;

Zigmond, MJ ;

Lin, MZ ;

Juo, P ;

Hu, LS ;

Anderson, MJ ;

Arden, KC ;

Blenis, J ;

Greenberg, ME .

CELL, 1999, 96 (06) :857-868

[5] Cell cycle and death control: long live Forkheads [J].

Burgering, BMT ;

Kops, GJPL .

TRENDS IN BIOCHEMICAL SCIENCES, 2002, 27 (07) :352-360

[6] Peripheral benzodiazepine receptor ligands: mitochondrial transmembrane potential depolarization and apoptosis induction in rat C6 glioma cells [J].

Chelli, B ;

Lena, A ;

Vanacore, R ;

Da Pozzo, E ;

Costa, B ;

Rossi, L ;

Salvetti, A ;

Scatena, F ;

Ceruti, S ;

Abbracchio, MP ;

Gremigni, V ;

Martini, C .

BIOCHEMICAL PHARMACOLOGY, 2004, 68 (01) :125-134

[7]

Chen RH, 1997, CELL GROWTH DIFFER, V8, P821

[8] Akt interacts directly with Smad3 to regulate the sensitivity to TGF-β-induced apoptosis [J].

Conery, AR ;

Cao, YN ;

Thompson, EA ;

Townsend, CM ;

Ko, TC ;

Luo, KX .

NATURE CELL BIOLOGY, 2004, 6 (04) :366-372

[9] Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1 [J].

Dijkers, PF ;

Medema, RH ;

Lammers, JWJ ;

Koenderman, L ;

Coffer, PJ .

CURRENT BIOLOGY, 2000, 10 (19) :1201-1204

[10] Transforming growth factor-β1 induces apoptosis in rat FaO hepatoma cells via cytochrome c release and oligomerization of Apaf-1 to form a ∼700-kd apoptosome caspase-processing complex [J].

Freathy, C ;

Brown, DG ;

Roberts, RA ;

Cain, K .

HEPATOLOGY, 2000, 32 (04) :750-760

← 1 2 3 →