Isoquercitrin Upregulates Aldolase C Through Nrf2 to Ameliorate OGD/R-Induced Damage in SH-SY5Y Cells

nm23 genes have been implicated in the suppression of tumour metastasis and cell motility; however, the biochemical mechanisms for these suppressions are not known. We have previously described the transfer of phosphate from the catalytic histidine residues of nm23 proteins to an aspartic or a glutamic residue on one or more 43 kDa proteins in detergent extracts of bovine brain membranes. To gain a better understanding of this transferase activity, we partly purified this 43 kDa protein and identified aldolases A and C as the major 43 kDa proteins present in the preparation. Aldolase was purified from brain cytosol; its phosphorylation by rat liver nm23 proteins and by recombinant human nm23-H1 was examined. The site of phosphorylation was identified as Asp-319 on aldolase C. The equivalent residue on aldolase A, a glutamic residue, was not phosphorylated. Aldolase C was rapidly phosphorylated by wild-type nm23-H1 but was not phosphorylated, or was phosphorylated very slowly, by either nm23-H1P96S or nm23-H1S120G, mutants of nm23-H1 that do not suppress cell motility. This is the first identification of a protein that is phosphorylated on an aspartic residue by nm23 proteins. The sequence around Asp-319 of aldolase C has some similarities to those around the histidine residues on ATP-citrate lyase and succinic thiokinase that are phosphorylated by nm23 proteins.

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New Proteins Found Interacting with Brain Metallothionein-3 Are Linked to Secretion

International Journal of Alzheimer s Disease ◽

10.4061/2011/208634 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Issam El Ghazi ◽

Bruce L. Martin ◽

Ian M. Armitage

Keyword(s):

Immunoaffinity Chromatography ◽

Glycolytic Metabolism ◽

Interacting Protein ◽

Aldolase C ◽

Growth Inhibitory Factor ◽

Protein Partners ◽

Growth Inhibitory ◽

Proposed Model ◽

The Brain ◽

Partner Proteins

Metallothionein 3 (MT-3), also known as growth inhibitory factor (GIF), exhibits a neuroinhibitory activity. Our lab and others have previously shown that this biological activity involves interacting protein partners in the brain. However, nothing specific is yet known about which of these interactions is responsible for the GIF activity. In this paper, we are reporting upon new proteins found interacting with MT-3 as determined through immunoaffinity chromatography and mass spectrometry. These new partner proteins—Exo84p, 14-3-3 Zeta,αandβEnolase, Aldolase C, Malate dehydrogenase, ATP synthase, and Pyruvate kinase—along with those previously identified have now been classified into three functional groups: transport and signaling, chaperoning and scaffolding, and glycolytic metabolism. When viewed together, these interactions support a proposed model for the regulation of the GIF activity of MT-3.

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