Pr. Bertrand Friguet

Pr. Bertrand Friguet

Laboratoire de Biologie et Biochimie Cellulaire du Vieillissement, UFR de Biologie,

Université Paris 7 – Denis Diderot, CC 71282, Place Jussieu, 75251 Paris Cedex 05, France.

Group’s experience:

This laboratory is currently studying the implication of protein modifications and maintenance systems in the ageing process. Proteins are indeed the target of post-translational modifications (e. g. oxidation, glycation, conjugation with lipid peroxidation products) that increase with age and affect their biological function.

We have experience in protein biochemistry, immunochemistry, molecular and cellular biology. In our group, antibodies aimed at recognizing modified proteins have been raised and we have recently observed the appearance of oxidized, glycated, lipid peroxidation product-conjugated and ubiquitinated proteins in ageing human keratinocytes, peripheral blood monocytes and rat myocytes.

oth an age-related down-regulation of the proteasome and the occurrence of age-associated modifications of its subunits. Declines in proteasome proteolytic activity have also been observed upon oxidative stress induced in cardiac ischemia-reperfusion injury or during UV irradiation of keratinocytes.

Treatment of human dermal fibroblasts by glyoxal that promotes the formation of glycated proteins (carboxymethyllysine) also resulted in proteasome inhibition. We are also interested in studying the implication in ageing of the protein repair enzyme system, peptide methionine sulfoxide reductases MsrA and MsrB.

We have previously reported that the gene expression and enzymatic activity of Msr A are decreasing with age and recently observed that both MsrA and MsrB are down-regulated during replicative senescence of WI 38 fibroblasts while mild oxidative stress was inducing their expression.

Personal involved:

1) Pr. B. Friguet, (M)group leader. Scientific supervision, expert in biochemistry.
2) Dr. I. Petropoulos, (M) assistant professor. Cellular and molecular biology expert.
3) Mrs. M. Perichon, (F) engineer. Cell culture, transfections and molecular biology.
4) Postdoctoral research fellow to be appointed to carry out the main part of the proposed studies.

Recent relevant publications:

1) I. Petropoulos, M. Conconi, X. Wang, B. Hoenel, F. Brégégère, Y. Milner & B. Friguet (2000) Increase of oxidatively modified protein is associated with a decrease of proteasome activity and content in aging epidermal cells. J. Gerontol. Biol. Sci. 55A : B220-B227.

2) I. Petropoulos, J. Mary, M. Perichon & B. Friguet (2001) The peptide methionine sulphoxide reductase : cloning of the cDNA and down-regulation of gene expression and enzyme activity during ageing. Biochem. J. 355 : 819-825.

3) A.L. Bulteau, P. Verbeke, I. Petropoulos, A. F. Chaffotte & B. Friguet (2001) Proteasome inhibition in glyoxal-treated fibroblasts and resistance of glycated glucose-6-phosphate dehydrogenase to 20S proteasome degradation in vitro. J. Biol. Chem. 276 : 45662-45668.

4) A. L. Bulteau, M. Moreau, C. Nizard & B. Friguet (2002). Impairment of proteasome function upon UVA- and UVB-irradiation of human keratinocytes. Free Radical Biol. Med. 32 : 1157-1170.

5) B. Friguet, A. L. Bulteau, M. Conconi & I. Petropoulos (2002). Redox control of the 20S proteasome. Method Enzymol. 353 : 253-262.