Hypoxia Induces the Activation of the Phosphatidylinositol 3-Kinase/Akt Cell Survival Pathway in PC12 Cells

Álvarez-Tejado, Miguel; Naranjo‐Suarez, Salvador; Jiménez, Concepción; Carrera, Ana C.; Landázuri, Manuel O.; Peso, Luis del

doi:10.1074/jbc.m011688200

Cited by 229 publications

(193 citation statements)

References 34 publications

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“…[31][32][33] However, in this study, the I/R ratio of the rats exposed to low barometric pressure hypoxia was significantly higher than that of the rats pretreated with 1000 ppm CO. And the activation of MAPKs, Akt, and eNOS induced by hypoxia was significantly weaker than that induced by 1000 ppm CO. In addition, I/R ratio was significantly lower in the rats pretreated with 1000 ppm CO than in those pretreated with 500 ppm CO, although the concentrations of HbCO in blood were not significantly different between the 2 groups (30.1% and 24.9% at 24 hours of inhalation, respectively).…”

Section: Discussioncontrasting

confidence: 44%

Carbon Monoxide Protects Against Cardiac Ischemia—Reperfusion Injury In Vivo via MAPK and Akt—eNOS Pathways

Fujimoto

Ohno

Ayabe

et al. 2004

ATVB

139

120

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Background-Carbon monoxide (CO) is postulated to protect tissues against several types of injuries. We investigated the role of CO in amelioration of cardiac ischemia-reperfusion injury in vivo and the mechanisms involved in it. Methods and Results-Rats inhaled CO (250 ppm, 500 ppm, or 1000 ppm) for 24 hours in a chamber after myocardial ischemia-reperfusion induced by occluding the left anterior descending coronary artery for 30 minutes. Pre-exposure to 1000 ppm of CO significantly reduced the ratio of infarct areas to risk areas and suppressed the migration of macrophages and monocytes into infarct areas, and the expression of tumor necrosis factor (TNF)-␣ in the heart; however, 250 ppm, 500 ppm of CO, or low barometric pressure hypoxia (0.5 atm) did not affect them. Exposure to 1000 ppm CO resulted in the activation of p38 mitogen-activated protein kinase (p38MAPK), protein kinase B␣(Akt), endothelial nitric oxide synthase (eNOS), and cyclic guanosine monophosphate (cGMP) in the myocardium. Inhibition of p38MAPK, PI3kinase, NO, and soluble guanylate cyclase with SB203580, wortmannin, N(G)-nitro-L-arginine methyl ester (L-NAME), and methylene blue, respectively, attenuated the cytoprotection by CO. Conclusion-CO has beneficial effects on cardiac ischemia-reperfusion injury; this effect is mediated by p38MAPK pathway and Akt-eNOS pathway, including production of cGMP.

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Section: Discussioncontrasting

confidence: 44%

Carbon Monoxide Protects Against Cardiac Ischemia—Reperfusion Injury In Vivo via MAPK and Akt—eNOS Pathways

Fujimoto

Ohno

Ayabe

et al. 2004

ATVB

139

120

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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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“…In these studies, virus-driven elevated Akt expression was shown to enhance survival of hydrogen peroxide-treated HeLa and NIH3T3 cells. These findings have been extended to other model systems of oxidative stress including treatment with neurotoxins known to generate ROS and models of oxidative preconditioning (Alvarez-Tejado et al, 2001;Han et al, 2001;Salinas et al, 2001).…”

Section: Pi3-kinase/akt Pathwaymentioning

confidence: 88%

Cellular response to oxidative stress: Signaling for suicide and survival*

Martindale

Holbrook

2002

Journal Cellular Physiology

2,100

1,596

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Reactive oxygen species (ROS), whether produced endogenously as a consequence of normal cell functions or derived from external sources, pose a constant threat to cells living in an aerobic environment as they can result in severe damage to DNA, protein, and lipids. The importance of oxidative damage to the pathogenesis of many diseases as well as to degenerative processes of aging has becoming increasingly apparent over the past few years. Cells contain a number of antioxidant defenses to minimize fluctuations in ROS, but ROS generation often exceeds the cell's antioxidant capacity, resulting in a condition termed oxidative stress. Host survival depends upon the ability of cells and tissues to adapt to or resist the stress, and repair or remove damaged molecules or cells. Numerous stress response mechanisms have evolved for these purposes, and they are rapidly activated in response to oxidative insults. Some of the pathways are preferentially linked to enhanced survival, while others are more frequently associated with cell death. Still others have been implicated in both extremes depending on the particular circumstances. In this review, we discuss the various signaling pathways known to be activated in response to oxidative stress in mammalian cells, the mechanisms leading to their activation, and their roles in influencing cell survival. These pathways constitute important avenues for therapeutic interventions aimed at limiting oxidative damage or attenuating its sequelae. Published 2002 Wiley‐Liss, Inc.

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Hypoxia Induces the Activation of the Phosphatidylinositol 3-Kinase/Akt Cell Survival Pathway in PC12 Cells

Cited by 229 publications

References 34 publications

Carbon Monoxide Protects Against Cardiac Ischemia—Reperfusion Injury In Vivo via MAPK and Akt—eNOS Pathways

Carbon Monoxide Protects Against Cardiac Ischemia—Reperfusion Injury In Vivo via MAPK and Akt—eNOS Pathways

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

Cellular response to oxidative stress: Signaling for suicide and survival*

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