Inactivation of Foxo3a and Subsequent Downregulation of PGC-1alpha Mediate Nitric Oxide-Induced Endothelial Cell Migration.

Background: FOXO3a is a protein that is an important regulator of oxidative stress by modulating antioxidants like catalase, influences aging, is a tumor repressor, reduced in Nrf2 animals and may contribute to fertility problems. It is found in higher amounts in centenarians, meaning those that live to a hundred years or more. Its activity can be effected by methylation and acetylation. (Wipedia-FOXO3a)

"Borniquel, S., García-Quintáns, N., Valle, I., Olmos, Y., Wild, B., Martínez-Granero, F., Soria, E., Lamas, S., and Monsalve, M. (2010). Inactivation of foxo3a and subsequent downregulation of pgc-1alpha mediate nitric oxide-induced endothelial cell migration. Molecular and cellular biology, 30(16):4035-4044."

CiteULike: Inactivation of Foxo3a and Subsequent Downregulation of PGC-1alpha Mediate Nitric Oxide-Induced Endothelial Cell Migration.:

TNFR1, TRPV1 and Inflammation.

Title: Reactive oxygen species mediate tnfr1 increase after trpv1 activation in mouse drg neurons.

Summary: It has been demonstrated the TNFR1 receptor is important for neuroinflammatory responses by MCP-1 and TNFR2 and Nf-kappaB signaling are important to antagonize TNFR1 signal-induced apoptosis. (Marchetti) Ma et al explains how Tnf-a causes nociceptive responses through TNFR1 activation. This study shows TNFR1 and ROS is absent in mice deficient of TRPV1. The conclusions from this study were that TRPV1 activation increases the TNFR1 receptor in culture DRG neurons through a ROS signaling pathway that can lead to pain generation during inflammation.

Notes:

• Foxo3a controls the increased expression of TNFR2 which prevents Tnf-mediated apoptosis (programmed cell death). (Ding)   
• Foxo3a is decreased in Nrf2 null mice. (Hu)

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• Antioxidant System Regulates Aging Genes and Loss Can Lead To Cell Death! 

Citations: Ma, F., Zhang, L., and Westlund, K. N. (2009). Reactive oxygen species mediate tnfr1 increase after trpv1 activation in mouse drg neurons. Molecular pain, 5(1):31+. http://www.citeulike.org/user/HEIRS/article/4934284
Ding, B., Kirkiles-Smith, N. C., and Pober, J. S. (2009). Foxo3a regulates oxygen-responsive expression of tumor necrosis factor receptor 2 in human dermal microvascular endothelial cells. J. Biol. Chem., 284(29):19331-19339. http://www.citeulike.org/user/HEIRS/article/5725120
Pradillo, J., Hurtado, O., Romera, C., Cardenas, A., Fernandeztome, P., Alonsoescolano, D., Lorenzo, P., Moro, M., and Lizasoain, I. (2006). Tnfr1 mediates increased neuronal membrane eaat3 expression after in vivo cerebral ischemic preconditioning. Neuroscience, 138(4):1171-1178. http://www.citeulike.org/user/HEIRS/article/5699676
Marchetti, L., Klein, M., Schlett, K., Pfizenmaier, K., and Eisel, U. L. (2004). Tumor necrosis factor (tnf)-mediated neuroprotection against glutamate-induced excitotoxicity is enhanced by n-methyl-d-aspartate receptor activation: Essential role of a tnf receptor 2-mediated phosphatidylinositol 3-kinase-dependent nf-kappab pathway. J. Biol. Chem., 279(31):32869-32881. http://www.citeulike.org/user/HEIRS/article/4080104
Hu, X., Roberts, J. R., Apopa, P. L., Kan, Y. W., and Ma, Q. (2006). Accelerated ovarian failure induced by 4-vinyl cyclohexene diepoxide in nrf2 null mice. 3:940-954. http://www.citeulike.org/user/HEIRS/article/5725231

Antioxidant System Regulates Aging Genes and Loss Can Lead To Cell Death!

MCP-1 neuroinflammatory processes are dependant on TNFR1. FOXO3a increases the activity of the TNFR2 promoter. Knock-down of the TNFR2 sensitizes microvascular endothelial cells to the activities of TNFR1 mediated apoptosis (programmed cell death). Endothelial dysfunction has been implicated as an important factor in the symptoms of many environmental diseases. FOXO3a is decreased in Nrf2 deficient cells. Other studies have identified FOXO3a as an important regulator of lifespan and aging. In ovarian cells, it has been shown that Nrf2 serves as a sensor and protects against harmful chemicals through a variety of ways including FOXO3a expression. Decreased Nrf2 will lead to a reduction of the FOXO3a modulation of TNFR2and consequentely may increase TNFR1-mediated apoptosis.

Ding, B., Kirkiles-Smith, N. C., and Pober, J. S. (2009). Foxo3a regulates oxygen-responsive expression of tumor necrosis factor receptor 2 in human dermal microvascular endothelial cells. J. Biol. Chem., 284(29):19331-19339. http://www.citeulike.org/user/HEIRS/article/5725120?updated=1252114581
GenAge for FOXO3.
Hu, X., Roberts, J. R., Apopa, P. L., Kan, Y. W., and Ma, Q. (2006). Accelerated ovarian failure induced by 4-vinyl cyclohexene diepoxide in nrf2 null mice. 3:940-954. http://www.citeulike.org/user/HEIRS/article/5725231