JNK Contributes to Hif-1α Regulation in Hypoxic Neurons

doi:10.3390/molecules15010114

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Molecules 2010, 15(1), 114-127; doi:10.3390/molecules15010114

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JNK Contributes to Hif-1α Regulation in Hypoxic Neurons

Xanthi Antoniou ¹ , Alessandra Sclip ¹ , Cristina Ploia ¹ , Alessio Colombo ¹ , Gautier Moroy ^2,† and Tiziana Borsello ¹^,*

¹ Istituto di Ricerche Farmacologiche \"Mario Negri\", Via La Masa 19, 20157 Milano, Italy ² Xigen SA, Rue des Terreaux 17, CH-1015 Lausanne, Switzerland ^† Current address: Molécules Thérapeutiques in silico (MTi), Inserm UMR-S 973, Université Paris Diderot, F-75013 Paris, France.

* Author to whom correspondence should be addressed.

Received: 5 November 2009; in revised form: 18 December 2009 / Accepted: 28 December 2009 / Published: 30 December 2009

(This article belongs to the Special Issue Neuroprotective Strategies)

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Abstract: Hypoxia is an established factor of neurodegeneration. Nowadays, attention is directed at understanding how alterations in the expression of stress-related signaling proteins contribute to age dependent neuronal vulnerability to injury. The purpose of this study was to investigate how Hif-1α, a major neuroprotective factor, and JNK signaling, a key pathway in neurodegeneration, relate to hypoxic injury in young (6DIV) and adult (12DIV) neurons. We could show that in young neurons as compared to mature ones, the protective factor Hif-1α is more induced while the stress protein phospho-JNK displays lower basal levels. Indeed, changes in the expression levels of these proteins correlated with increased vulnerability of adult neurons to hypoxic injury. Furthermore, we describe for the first time that treatment with the D-JNKI1, a JNK-inhibiting peptide, rescues adult hypoxic neurons from death and contributes to Hif-1α upregulation, probably via a direct interaction with the Hif-1α protein.

Keywords: JNK; HIF-1α; hypoxia; neurons

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MDPI and ACS Style

Antoniou, X.; Sclip, A.; Ploia, C.; Colombo, A.; Moroy, G.; Borsello, T. JNK Contributes to Hif-1α Regulation in Hypoxic Neurons. Molecules 2010, 15, 114-127.

AMA Style

Antoniou X., Sclip A., Ploia C., Colombo A., Moroy G., Borsello T. JNK Contributes to Hif-1α Regulation in Hypoxic Neurons. Molecules. 2010; 15(1):114-127.

Chicago/Turabian Style

Antoniou, Xanthi; Sclip, Alessandra; Ploia, Cristina; Colombo, Alessio; Moroy, Gautier; Borsello, Tiziana. 2010. "JNK Contributes to Hif-1α Regulation in Hypoxic Neurons." Molecules 15, no. 1: 114-127.

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