The matrix metalloproteinases (MMPs) form an enzyme family of which gelatinase B (MMP-9) represents the largest and most complex member. We focus here on the biochemical properties, regulation, and functions of gelatinase B. The tight regulation of gelatinase B activity is highly complex and is established at five different levels. The transcription of the gelatinase B-gene depends on various cis-elements in its gene promotor and is induced or repressed by a large variety of soluble factors, including cytokines, growth factors, and hormones and by cellular contacts acting through specific signaling pathways. The specific regulation of its secretion occurs in cells storing gelatinase B in granules. After secretion, progelatinase B must be activated through an activation network. The enzyme activity is further regulated by inhibition and by other mechanisms, such as fine-tuning and stabilization by glycosylation. The ability of gelatinase B to degrade components of the extracellular matrix and to regulate the activity of a number of soluble proteins confers an important role in various physiological and pathological processes. These include reproduction, growth, development, inflammation, and vascular and proliferative diseases.
Summary The phytoalexin‐deficient Arabidopsis mutant pad3‐1, which is affected in the production of the indole‐type phytoalexin camalexin, has previously been shown not to display altered susceptibility to either the bacterium Pseudomonas syringae (Glazebrook & Ausubel 1994; Proc. Natl. Acad. Sci. USA, 91: 8955–8959) or the biotrophic fungi Peronospora parasitica (Glazebrook et al. 1997; Genetics, 146: 381–392) and Erysiphe orontii (Reuber et al. 1998; Plant J. 16: 473–485). We now show that this mutant is markedly more susceptible than its wild‐type parental line to infection by the necrotrophic fungus Alternaria brassicicola, but not to Botrytis cinerea. A strong camalexin response was elicited in wild‐type plants inoculated with either Alternaria brassicicola or Botrytis cinerea, whereas no camalexin could be detected in pad3‐1 challenged with these fungi. Hence, PAD3 appears to be a key determinant in resistance to at least A. brassicicola. The induction of salicylate‐dependent and jasmonate/ethylene‐dependent defense genes was not reduced in Alternaria‐challenged pad3‐1 plants compared to similarly treated wild‐type plants. Camalexin production could not be triggered by exogenous application of either salicylate, ethylene or jasmonate and was not, or not strongly, reduced in mutants with defects in perception of these defense‐related signal molecules. Camalexin‐production appears to be controlled by a pathway that exhibits little cross‐talk with salicylate‐, ethylene‐ and jasmonate‐dependent signalling events.
Nanosized objects, such as nanoparticles and other drug carriers used in nanomedicine, once in contact with biological environments are modified by adsorption of biomolecules on their surface. The presence of this corona strongly affects the following interactions at cell and organism levels. It has been shown that corona proteins can be recognized by cell receptors. However, it is not known whether the composition of this acquired layer can also affect the mechanisms nanoparticles use to enter cells. This is of particular importance when considering that the same nanoparticles can form different coronas for instance in vitro when exposed to cells in different serum amounts or in vivo depending on the exposure or administration route. Thus, in this work, different coronas were formed on 50 nm silica by exposing them to different serum concentrations. The uptake efficiency in HeLa cells was compared, and the uptake mechanisms were characterized using transport inhibitors and RNA interference. The results showed that the nanoparticles were internalized by cells via different mechanisms when different coronas were formed, and only for one corona condition was uptake mediated by the LDL receptor. This suggested that coronas of different composition can be recognized differently by cell receptors, and this in turn leads to internalization via different mechanisms. Similar studies were performed using other cells, including A549 cells and primary HUVEC, and different nanoparticles, namely 100 nm liposomes and 200 nm silica. Overall, the results confirmed that the corona composition can affect the mechanisms of nanoparticle uptake by cells.
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