HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 27, 24368-24375, July 5, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/27/24368    most recent M201924200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lu, C. Articles by Mattson, M. P. Search for Related Content PubMed PubMed Citation Articles by Lu, C. Articles by Mattson, M. P. Social Bookmarking                      What's this?

The Lipid Peroxidation Product 4-Hydroxynonenal Facilitates Opening of Voltage-dependent Ca²⁺ Channels in Neurons by Increasing Protein Tyrosine Phosphorylation^*

Chengbiao Lu, Sic L. Chan, Weiming Fu, and Mark P. Mattson^§¶

From the  Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, Maryland 21224 and ^§ Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Calcium influx through voltage-dependent calcium channels (VDCCs) mediates a variety of functions in neurons and other excitable cells, but excessive calcium influx through these channels can contribute to neuronal death in pathological settings. Oxyradical production and membrane lipid peroxidation occur in neurons in response to normal activity in neuronal circuits, whereas excessive lipid peroxidation is implicated in the pathogenesis of of neurodegenerative disorders. We now report on a specific mechanism whereby lipid peroxidation can modulate the activity of VDCCs. The lipid peroxidation product 4-hydroxy-2,3-nonenal (4HN) enhances dihydropyridine-sensitive whole-cell Ca²⁺ currents and increases depolarization-induced increases of intracellular Ca²⁺ levels in hippocampal neurons. Prolonged exposure to 4HN results in neuronal death, which is prevented by treatment with glutathione and attenuated by the L-type Ca²⁺ channel blocker nimodipine. Tyrosine phosphorylation of 1 VDCC subunits is increased in neurons exposed to 4HN, and studies using inhibitors of tyrosine kinases and phosphatases indicate a requirement for tyrosine phosphorylation in the enhancement of VDCC activity in response to 4HN. Phosphorylation-mediated modulation of Ca²⁺ channel activity in response to lipid peroxidation may play important roles in the responses of neurons to oxidative stress in both physiological and pathological settings.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				K. Fukuda, S. S. Davies, T. Nakajima, B.-H. Ong, S. Kupershmidt, J. Fessel, V. Amarnath, M. E. Anderson, P. A. Boyden, P. C. Viswanathan, et al. Oxidative Mediated Lipid Peroxidation Recapitulates Proarrhythmic Effects on Cardiac Sodium Channels Circ. Res., December 9, 2005; 97(12): 1262 - 1269. [Abstract] [Full Text] [PDF]

				P. V. Usatyuk and V. Natarajan Role of Mitogen-activated Protein Kinases in 4-Hydroxy-2-nonenal-induced Actin Remodeling and Barrier Function in Endothelial Cells J. Biol. Chem., March 19, 2004; 279(12): 11789 - 11797. [Abstract] [Full Text] [PDF]

				Y. V. Bobkov and B. W. Ache Calcium Sensitivity of a Sodium-Activated Nonselective Cation Channel in Lobster Olfactory Receptor Neurons J Neurophysiol, November 1, 2003; 90(5): 2928 - 2940. [Abstract] [Full Text] [PDF]