Cystamine restores GSTA3 levels in Vanin-1 null mice.
Free cysteamine levels in mouse tissues have been strictly correlated to the presence of membrane-bound pantetheinase activity encoded by Vanin-1. Vanin-1 is involved in many biological processes in mouse, from thymus homing to sexual development. Vanin-1 -/- mice are fertile and grow and develop normally; they better control inflammation and most of the knockout effects were rescued by cystamine treatment. Gene structure analysis showed the presence of an oxidative stimuli-responsive ARE-like sequence in the promoter. In this paper we investigate antioxidant-detoxifying enzymatic activities at the tissue level, comparing Vanin-1 -/- and wild-type mice. In Vanin-1 null animals we pointed out a decrease in the Se-independent glutathione peroxidase activity. The decrease in enzymatic activity appeared to be correlated to an impairment of GST isoenzyme levels. In particular a significant drop in GSTA3 together with a minor decrement in GSTM1 and an increase in GSTP1 levels was detected in Vanin-1 -/- livers. Cystamine administration to Vanin-1 -/- mice restored specifically GSTA3 levels and the corresponding enzymatic activity without influencing protein expression. A possible role of cystamine on protein stability/folding can be postulated.
Di Leandro
Luana
L
Dipartimento di Biologia di Base e Applicata, Università degli Studi, L'Aquila, Italy.
Maras
Bruno
B
Schininà
M Eugenia
ME
Dupré
Silvestro
S
Koutris
Ilias
I
Martin
Florent M
FM
Naquet
Philippe
P
Galland
Franck
F
Pitari
Giuseppina
G
D000581:Amidohydrolases; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D003538:Cystamine / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D058851:GPI-Linked Proteins; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D007527:Isoenzymes; D011837:Radiation-Protective Agents; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D000581:Amidohydrolases; C022314:pantetheinase; D003538:Cystamine