Oxidative Medicine and Cellular Longevity

Oxidative Medicine and Cellular Longevity / 2010 / Article

Open Access

Volume 3 |Article ID 835947 | https://doi.org/10.4161/oxim.3.5.13296

Margot Lawton, Ming Tong, Fusun Gundogan, Jack R. Wands, Suzanne M. de la Monte, "Aspartyl-(asparaginyl) β-Hydroxylase, Hypoxia-Inducible Factor-1α and Notch Cross-Talk in Regulating Neuronal Motility", Oxidative Medicine and Cellular Longevity, vol. 3, Article ID 835947, 10 pages, 2010. https://doi.org/10.4161/oxim.3.5.13296

Aspartyl-(asparaginyl) β-Hydroxylase, Hypoxia-Inducible Factor-1α and Notch Cross-Talk in Regulating Neuronal Motility

Received22 Jul 2010
Accepted09 Aug 2010

Abstract

Aspartyl-(Asparaginyl)-β-Hydroxylase (AAH ) promotes cell motility by hydroxylating Notch. Insulin and insulin-like growth factor, type 1 (IGF-I) stimulate AAH through Erk MAP K and phosphoinositol-3-kinase-Akt (PI3K-Akt). However, hypoxia/oxidative stress may also regulate AAH . Hypoxia-inducible factor-1alpha (HIF-1α) regulates cell migration, signals through Notch, and is regulated by hypoxia/oxidative stress, insulin/IGF signaling and factor inhibiting HIF-1α (FIH) hydroxylation. To examine cross-talk between HIF-1α and AAH , we measured AAH , Notch-1, Jagged-1, FIH, HIF-1α, HIF-1β and the hairy and enhancer of split 1 (HE S-1) transcription factor expression and directional motility in primitive neuroectodermal tumor 2 (PNET2) human neuronal cells that were exposed to H2O2 or transfected with short interfering RNA duplexes (siRNA) targeting AAH , Notch-1 or HIF-1α. We found that: (1) AAH , HIF-1α and neuronal migration were stimulated by H2O2; (2) si-HIF-1α reduced AAH expression and cell motility; (3) si-AAH inhibited Notch and cell migration, but not HIF-1α and (4) si-Notch-1 increased FIH and inhibited HIF-1α. These findings suggest that AAH and HIF-1α crosstalk within a hydroxylation-regulated signaling pathway that may be transiently driven by oxidative stress and chronically regulated by insulin/IGF signaling.

Copyright © 2010 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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