Inflammation increases MMP levels via PGE2 in human vascular wall and plasma of obese women.

BACKGROUND AND OBJECTIVES: Matrix metalloproteinases (MMPs) are involved in several inflammatory processes including obesity-related vascular diseases and graft failure of coronary artery (CA) bypass grafts [internal mammary artery (IMA), saphenous vein (SV)]. In these inflammatory conditions, the release of prostaglandin E2 (PGE2) is increased via the activity of inducible microsomal PGE synthase-1 (mPGES-1). Our aim was to investigate whether MMPs and their endogenous inhibitor (TIMPs) may be regulated by PGE2 under inflammatory conditions in human vasculature and perivascular adipose tissue (PVAT), as well as in plasma of obese patients. METHODS: MMP-1,-2 and TIMP-1,-2 densities were measured in human plasma (n = 68) as well as in supernatants of human vascular wall (IMA n = 16, SV n = 14, CA n = 13) and their PVAT. The effects of inflammation and mPGES-1 inhibitor (Compound III, 10 µM) on MMPs regulation were evaluated. The correlations between PGE2 and several parameters were calculated in plasma from patients with or without obesity. RESULTS: The vascular wall and PVAT from SV exhibited the greatest MMP-1,-2 release. An increase of MMP-1,-2 and/or a decrease of TIMP-1 quantities have been detected under inflammation only in vascular wall not in PVAT. These changes under inflammation were completely reversed by inhibition of mPGES-1. In obesity, C-reactive protein (CRP), biomarker of inflammation, and PGE2 levels were increased. PGE2 contents were positively correlated with some anthropometric parameters and plasmatic CRP in both genders, while the correlation with the plasmatic MMP-1 density was significant only in women. CONCLUSIONS: The greater MMP activity observed in SV may contribute to the increased prevalence of graft failure. Under inflammation, the greater mPGES-1 and PGE2 levels lead to enhanced MMP activity in human vascular walls. The positive association between PGE2 and MMP-1 or CRP has been observed in plasma of women. We suggest that mPGES-1 inhibitors could prevent graft failure and obesity-related vascular remodeling mostly in women.

[The therapeutic contribution of proteomic approaches in cancers]. / L'apport thérapeutique des approches protéomiques dans les cancers.

Up to now, there are no protein tumor markers with a specificity and sensitivity sufficient to have a utility in prognosis and early diagnosis of cancer. Recent advances in proteomics approaches have led to the identification of novel tumor markers of cancer that may have a utility in screening strategies and treatment. The purpose of the current review is to describe the major advances in cancer proteomics, especially those related to the study of serum biomarkers, immune-related responses (autoantibodies) and alterations in cellular proteins.

Proteomics approaches: new technologies and clinical applications in breast carcinomas.

UNLABELLED: Breast cancer is the most diagnosed cancer in women, accounting for approximately 40,000 deaths annually in the USA. In Tunisia, the incidence of breast cancer is approximately 19 new cases per 100,000 women per year. Significant advances have been made in the areas of detection and treatment, but a significant number of breast cancers are detected late. The advent of proteomics provides the hope of discovering novel biological markers that can be used for early detection, prognosis, diagnosis, and therapy. Several proteomics technologies have been used to uncover molecular mechanisms associated with breast. INTRODUCTION: Breast cancer is a major health problem and one of the leading causes of death among women worldwide. Its incidence is steadily rising in developing countries. In Tunisia, the incidence of breast cancer is approximately 19 new cases per 100,000 women per year(1). Invasive carcinomas represent 70-80% of all breast cancer and among these, infiltrating ductal carcinomas (IDCA) are the most aggressive forms and have a poor prognosis(2). Histopathologically identical breast cancers show a different biological behavior in terms of aggressiveness, progression, and response to therapy. Thus, there is a great need for new breast cancer biomarkers that might help detect this cancer at an earlier stage, to uncover prognostically distinct subclasses, and to provide best individual treatment(2). Currently, the search for specific cancer-related alterations are largely carcinoma at the global level to discover protein patterns that distinguish disease and disease-free states with high sensitivity and specificity. Two dimensional gel electrophoresis coupled with mass spectrometry constitute a new proteomics based paradigm for detecting disease in pathology specimens and monitoring disease response to therapy. This review describes these proteomics technologies and their application in the analysis of breast carcinoma.

Analysis by two-dimensional electrophoresis of the effect of salt stress on the polypeptide patterns in roots of a salt-tolerant and a salt-sensitive cultivar of wheat.

The effect of salt stress on the polypeptide levels in roots of two wheat (Triticum durum) cultivars with different sensitivity to NaCl (cv. Ben Bachir, sensitive; cv. Chili, tolerant), was examined by two-dimensional polyacrylamide gel electrophoresis. Blue-stained gels were analyzed by visual inspection to identify changes that resulted when seedlings were grown in the presence of 200 mM NaCl for four days. Although the protein patterns for control and salt-stressed seedlings were qualitatively similar, the net synthesis of a 26 kDa polypeptide was significantly changed. This observation was mainly noticeable in the more tolerant cultivar. With the intention of identifying its function, the NH2-terminal of this polypeptide was sequenced. A 20 amino acid sequence was obtained and compared to sequences available in different databases. Possible roles of this polypeptide, depending on the homologies of its amino acid sequence with known proteins, in salinity tolerance are discussed.

Phytohormone regulation of isoperoxidases in Catharanthus roseus suspension cultures.

Peroxidase (POD) activity was investigated in Catharanthus roseus cell suspensions cultured under different hormonal conditions. Depletion of 2,4-dichlorophenoxyacetic acid (2,4-D) from the culture medium enhanced POD activity in cells and spent medium. Addition of phytohormones, in particular the auxin 2,4-D, reduced POD activity in medium and cellular compartments and enhanced ionically cell-wall bound POD. The differential modulation of POD is due to hormone effects on synthesis and/or accumulation of POD, rather than on the secretion process. Qualitative analysis showed that 2,4-D, but not cytokinins, regulated the synthesis of a basic isoform. The cytokinin treatment seemed to affect acidic rather than basic isoforms. The presence of basic POD is correlated with the capacity of cells to produce indole alkaloids. The major extracellular basic isoperoxidase was purified to homogeneity from culture medium of Catharanthus roseus cell suspensions. The isolated peroxidase is a haem protein with a M(r) of 33,000 and a pI close to 9. The effect of pH on peroxidase activity was studied using guaiacol as substrate and the optimum pH determined at 25 degrees was 6.0. This enzyme acted on guaiacol, 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), o-dianisidine, o-phenylenediamine (o-PD) and pyrogallol, but had no effect on syringaldazine or coniferyl alcohol substrates.