Hypoxia and CoCl2 protect HepG2 cells against serum deprivation- and t-BHP-induced apoptosis: a possible anti-apoptotic role for HIF-1

Piret, Jean-Pascal; Lecocq, Christophe; Toffoli, Sébastien; Ninane, Noëlle; Raes, Martine; Michiels, Carine

doi:10.1016/j.yexcr.2004.01.024

Cited by 76 publications

(82 citation statements)

References 31 publications

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“…Furthermore, overexpression of REDD1 under normoxic conditions protected cells from UV-induced cell death as well (Figure 6c). Even though both pro-and antiapoptotic effects of hypoxia and HIF-1a are described (Piret et al, 2002b), it is known that hypoxia (or induction of HIF-1a by CoCl 2 ) can reduce the sensitivity of cells to apoptosis (Piret et al, 2002a(Piret et al, , 2004. Similarly, overexpression of HIF-1a was shown to increase cellular resistance to apoptosis (Akakura et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Cells expressing full-length REDD1, a C-terminally truncated version of REDD1 or constitutively active PI 3-kinase (p110*) were more resistant to UV-induced apoptosis as indicated by a reduced cleaved PARP signal compared to cells expressing a catalytically inactive mutant of p110 (K to R) or a N-terminally truncated version of REDD1 (Figure 6c). These data suggest that increased REDD1 expression is sufficient for mediating the known hypoxia-induced antiapoptotic response (Piret et al, 2002a(Piret et al, , 2004Zhang et al, 2003). To test whether loss of HIF-1a or REDD1 function sensitizes cells to UVinduced apoptosis we transfected HaCaT cells with HIF-1a or REDD1-specific GBs.…”

Section: Redd1 Function Is Necessary and Sufficient To Mediate The Hymentioning

confidence: 99%

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REDD1 integrates hypoxia-mediated survival signaling downstream of phosphatidylinositol 3-kinase

Schwarzer¹,

Tondera²,

Arnold³

et al. 2004

Oncogene

119

108

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Cancer cells frequently evade apoptosis during tumorigenesis by acquiring mutations in apoptotic regulators. Chronic activation of the PI 3-kinase-Akt pathway through loss of the tumor suppressor PTEN is one mechanism by which these cells can gain increased protection against apoptosis. We report here that REDD1 (RTP801) can act as a transcriptional downstream target of PI 3-kinase signaling in human prostate cancer cells (PC-3). REDD1 expression is markedly reduced in PC-3 cells treated with LY294002 (LY) or Rapamycin and strongly induced under hypoxic conditions in a hypoxiainducible factor-1 (HIF-1)-dependent manner. Loss of function studies employing antisense molecules or RNA interference indicate that REDD1 is essential for invasive growth of prostate cancer cells in vitro and in vivo. Reduced REDD1 levels can sensitize cells towards apoptosis, whereas elevated levels of REDD1 induced by hypoxia or overexpression desensitize cells to apoptotic stimuli. Taken together our data designate REDD1 as a novel target for therapeutic intervention in prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Redd1 Function Is Necessary and Sufficient To Mediate The Hymentioning

confidence: 99%

REDD1 integrates hypoxia-mediated survival signaling downstream of phosphatidylinositol 3-kinase

Schwarzer¹,

Tondera²,

Arnold³

et al. 2004

Oncogene

119

108

View full text Add to dashboard Cite

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“…Cell cycle arrest (Goda et al, 2003) Decreased Proapoptotic (Carmeliet et al, 1998) Increased Antiapoptotic (Piret et al, 2004) Decreased Enhanced glycolysis (Semenza et al, 1994) Increased Angiogenesis (Carmeliet et al, 1998) Decreased (Gorski et al, 1999) HIF-1-deficient tumour cells (Moeller et al, 2004). In line with this finding, the vasculature of HIF-1-deficient tumours undergoes significantly more regression following irradiation than does the vasculature of their wild-type controls (Moeller et al, 2005b).…”

Section: Hif-1-mediated Effect Potential Impact On Radiosensitivitymentioning

confidence: 91%

HIF-1 and tumour radiosensitivity

2006

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“…Hif-1a promotes cell death through an increase in p53 or other proapoptotic proteins such as Bcl-2/E1B 19 kDa interacting protein 3 (BNIP3) or BNIP3L (NIX) (Carmeliet et al, 1998;Bruick, 2000;Guo et al, 2001;Sowter et al, 2001). Under most circumstances however, Hif-1a promotes survival of cancer or endothelial cells under hypoxic condition and also protects against apoptosis induced by serum deprivation or by anticancer agents (Alvarez-Tejado, 2001; Sasabe et al, 2005;Piret et al, 2004;Kim et al, 2004a, b;Zhang et al, 2004). Hif-1a exerts its antiapoptotic function by transcriptional activation of antiapoptotic proteins, for example, those of the Bcl-2 family or inhibitor of apoptosis 'IAPs', or by alterations in cellular energy metabolism through increased glucose uptake and glycolysis (Mathupala et al, 2001;Park et al, 2002;Dong et al, 2003;Zhang et al, 2004;Blum et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Role of hypoxia inducible factor-1 alpha in modulation of apoptosis resistance

et al. 2006

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Hypoxia inducible factor-1 (HIF-1) is the major transcription factor and key regulator of adoptive responses to hypoxia. Although it usually promotes tumor cell survival under hypoxia, it has also been implied to trigger apoptosis. Although the impact of hypoxia has been extensively studied in many adult solid tumors, its role in most childhood tumors, for example, in rhabdomyosarcoma (RMS) or Ewing sarcoma (ES), has not yet been addressed. Here, we report that hypoxia protects A204 RMS and A673 ES cells against anticancer drug-or tumor necrosis factor-related apoptosis-inducing ligandinduced apoptosis and that Hif-1a plays a key role in conferring apoptosis resistance under hypoxia. Although a functional HIF-1 pathway and proapoptotic proteins such as p53 and Bcl-2/E1B 19 kDa interacting protein 3 were activated under hypoxia in both A204 RMS and A673 ES cells, these cells remained refractory to apoptosis. Concomitant analysis of antiapoptotic proteins revealed that hypoxia induced expression of Bcl-2 and inhibitor of apoptosis proteins (IAP)-2 as well as proteins associated with anaerobic metabolism such as the glucose transporter protein GLUT-1 and the glycolytic enzyme Aldolase A. Specific downregulation of Hif-1a by RNA interference significantly enhanced apoptosis under hypoxia by preventing the hypoxia-mediated increase in GLUT-1 expression without altering expression levels of the antiapoptotic proteins Bcl-2 or cIAP-2. Moreover, glucose deprivation-induced apoptosis of A204 RMS and A673 ES cells was inhibited under hypoxic conditions in a Hif-1a-dependent manner. As GLUT-1 was induced via Hif-1a under hypoxia in A204 RMS and A673 ES, these findings suggest that the Hif-1a-mediated increase in glucose uptake plays an important role in conferring apoptosis resistance. Thus, hypoxia-inducible genes may represent novel targets for therapeutic intervention in some pediatric tumors, which warrants further investigation.

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Hypoxia and CoCl2 protect HepG2 cells against serum deprivation- and t-BHP-induced apoptosis: a possible anti-apoptotic role for HIF-1

Cited by 76 publications

References 31 publications

REDD1 integrates hypoxia-mediated survival signaling downstream of phosphatidylinositol 3-kinase

REDD1 integrates hypoxia-mediated survival signaling downstream of phosphatidylinositol 3-kinase

HIF-1 and tumour radiosensitivity

Role of hypoxia inducible factor-1 alpha in modulation of apoptosis resistance

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