Matrix metalloproteinases (MMPs) are a major group of enzymes that regulate cell-matrix composition. MMP genes show a highly conserved modular structure. Ample evidence exists on the role of MMPs in normal and pathological processes, including embryogenesis, wound healing, inflammation, arthritis, cardiovascular diseases, pulmonary diseases and cancer. The expression patterns of MMPs have interesting implications for the use of MMP inhibitors as therapeutic agents. Insights might be gained as to the preference for a general MMP inhibitor as opposed to an inhibitor designed to be specific for certain MMP family members as it relates to a defined disease state, and may give clues to potential side effects. The signalling pathways that lead to induction of expression of MMPs are still incompletely understood, but certain patterns are beginning to emerge. Regarding inhibition of MMP expression at the level of kinase pathways, it is possible that selective chemical inhibitors for distinct signalling pathways (e.g. MAPK, PKC) will hopefully, soon be available for initial clinical trials. Overexpression of selective dual specificity MAPK phosphatases have been shown to prevent MMP promoter activation which could also be used as a novel strategy to prevent activation of AP-1 and ETS transcription factors and MMP promoters in vivo. Interactions between members of different transcription factors provide fine-tuning of the transcriptional regulation of MMP promoter activity. MMPs play a crucial role in tumor invasion. Although the expression of MMPs in malignancies has been studied widely, the specific role of distinct MMPs in the progression of cancer may be more complex than has been assumed. For example, it has recently been shown that MMP-3, MMP-7, MMP-9 and MMP-12 can generate angiostatin from plasminogen, indicating that their expression in peritumoral area may in fact serve to limit angiogenesis and thereby inhibit tumor growth and invasion. The recent view about the role of stromal cells in the progression of cancer cell growth and metastasis is particularly interesting, and additional studies about the regulation of MMP gene expression and activity in malignancies are needed to understand the role and regulation of MMPs in tumor cell invasion.

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Generation of reactive oxygen species (ROS) is a normal process in the life of aerobic organisms. Under physiological conditions, these deleterious species are mostly removed by the cellular antioxidant systems, which include antioxidant vitamins, protein and non-protein thiols, and antioxidant enzymes. Since the antioxidant reserve capacity in most tissues is rather marginal, strenuous physical exercise characterized by a remarkable increase in oxygen consumption with concomitant production of ROS presents a challenge to the antioxidant systems. An acute bout of exercise at sufficient intensity has been shown to stimulate activities of antioxidant enzymes. This could be considered as a defensive mechanism of the cell under oxidative stress. However, prolonged heavy exercise may cause a transient reduction of tissue vitamin E content and a change of glutathione redox status in various body tissues. Deficiency of antioxidant nutrients appears to hamper antioxidant systems and augment exercise-induced oxidative stress and tissue damage. Chronic exercise training seems to induce activities of antioxidant enzymes and perhaps stimulate GSH levels in body fluids. Recent research suggest that supplementation of certain antioxidant nutrients are necessary for physically active individuals.

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An efficient in vitro screening method has been developed for mulberry ( Morus spp. ) to screen salinity-tolerant genotypes from a large population. Axillary buds from field-grown plants were cultured on MS medium containing five different concentrations (0.0%, 0.25%, 0.5%, 0.75% and 1.00%) of sodium chloride (NaCl) in order to study the shoot growth pattern. Rooting was also tested at four different concentrations of NaCl (0.0%, 0.1%, 0.2% and 0.3.%). NaCl has been found to inhibit the growth and development of mulberry shoots and roots in vitro. The survivability of the axillary buds of the genotypes tested was reduced from 83.7% for the controls to 6.1% in 1.0% NaCl. The average number of roots developed by the genotypes ranged from 11.9 (controls) to 0.2 (0.3% NaCl). Out of the 63 genotypes tested, only seven--Rotundiloba, English black, Kolitha-3, Berhampore-A, Kajli, BC(2)59 and C776--developed roots in 0.3% NaCl. Root growth was also reduced drastically from 1.8 cm for the controls to 0.1 cm in 0.3% NaCl. To test the reproducibility of the results in soil, five tolerant and two susceptible genotypes, identified in this in vitro study, were selected and tested under ex vitro conditions. The significant correlation coefficients obtained between the performances of these genotypes under both types of cultural conditions revealed that in vitro screening of mulberry through axillary bud culture is an easy and efficient method to identify salt-adapted genotypes within a limited space and time period.

Exposure of bovine pulmonary arterial endothelial cells to the oxidant tert-butyl hydroperoxide (t-bu-OOH) caused a dose-dependent increase in the release of [14C]arachidonic acid and synthesis of the cyclooxygenase products, thromboxane, prostaglandin E2, prostaglandin D2, and prostacyclin. There was no detectable production of peptide leukotrienes before or after administration of t-bu-OOH. Pretreatment with the oxygen radical scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidino radical (HTP) or the antioxidants vitamin E and dithiothreitol prevented the increased arachidonic acid (AA) release caused by t-bu-OOH. t-bu-OOH increased the activity of phospholipase A2 by increasing its apparent maximum velocity without affecting its Michaelis constant. The increased AA release caused by t-bu-OOH did not appear to require new RNA or protein synthesis, because pretreatment of the cells with actinomycin D or cycloheximide did not reduce the increased release of AA or activation of phospholipase A2 caused by t-bu-OOH. Dexamethasone pretreatment of the cells prevented the increase in phospholipase A2 activity, and AA release produced by t-bu-OOH. t-bu-OOH increased the activity of phospholipase A2 and release of AA in both the presence and absence of extracellular calcium (Ca2+). Pretreatment with a nominal Ca2+-free buffer, the Ca2+ chelator ethylene glycolbis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, nifedipine, or verapamil did not reduce t-bu-OOH-stimulated AA release. In contrast, treatment with the intracellular Ca2+ chelator 8-N,N-diethyamino octyl 3,4,5-trimethoxybenzoate (TMB-8) prevented t-bu-OOH-stimulated AA release in both the presence and absence of extracellular Ca2+. Treatment with calmodulin antagonists also prevented the increased release of AA caused by t-bu-OOH.