Molecular analysis of homocysteic acid-induced neuronal stress

Journal of Proteome Research
Susanne SommerAndré Schrattenholz

Abstract

Hyperhomocysteinemia is a risk factor for vascular and neuronal lesions often observed with concomitant high levels of homocysteic acid. In contrast to homocysteine, homocysteic acid induces calcium influx into neurons, with characteristics of an excitotoxic glutamatergic agonist at elevated concentrations. On the molecular level this is correlated to fast modifications of proteins (phosphorylation and proteolysis). Within the homocysteic acid induced molecular signature we focused in more detail on phosphorylation of two proteins implicated as risk factors in schizophrenia and neurodegeneration: Dihydropyrimidinase related protein and 14-3-3 protein isoforms. Among the identified proteins there are known chaperones and oxidative metabolism enzymes, but a few are new in context of neuronal stress: Lasp-1, a vitamin D associated factor and an expressed sequence with features of a Rho GDP dissociation inhibitor. Moreover, we detect a specific proteolytic processing of heat shock protein 70 and proteindisulfide isomerase, which is abolished by vitamins (folic acid, vitamin B12, and vitamin B6), which also decrease elevated intracellular calcium levels induced by homocysteic acid.

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Citations

Sep 13, 2008·Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz·M KlemmA Schrattenholz
Apr 7, 2015·Cellular Signalling·Giuliano Molinari
Jun 23, 2007·The Journal of Steroid Biochemistry and Molecular Biology·Michael A Cahill
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May 10, 2005·Proteomics·Oliver KleinerJasminka Godovac-Zimmermann
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Mar 2, 2010·Experimental Gerontology·Karlfried GroebeAndré Schrattenholz
Jun 1, 2004·Alternatives to Laboratory Animals : ATLA·André SchrattenholzMichael Cahill
Jan 23, 2021·International Journal of Molecular Sciences·Hendrik NieraadGerd Geisslinger
May 10, 2008·Journal of Proteome Research·Vukić SoskićAndré Schrattenholz
Oct 6, 2010·Journal of Proteome Research·Karlfried GroebeAndre Schrattenholz

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