A sticky situation: CCN1 promotes both proliferation and apoptosis of cancer cells

Connective tissue growth factor (CTGF/CCN2) is overexpressed in diabetes. Diabetic rats possess myocardial and cardiomyocyte hypertrophy. In a recent report, Wang and colleagues (Am J Physiol Cell Physiol. 2009 Jul 22. [Epub ahead of print]) show that CCN2 directly mediates cardiomyocyte hypertrophy as well as that induced by high glucose and fatty acid. CCN2 acted via the TrkA receptor. These data are the subject of this commentary, and emphasize that CCN2 may be an excellent target for therapy in diabetes.     

Growth and water relations in a central North Carolina population of <Emphasis Type="Italic">Microstegium vimineum</Emphasis> (Trin.) A. Camus

The ability of an invasive plant to occupy new areas is often attributed to both morphological and physiological plasticities that allow them to remain viable over a wide range of environmental conditions. Studies addressing the ecological requirements of Microstegium vimineum often consider soil moisture or soil moisture along with other factors as important explanatory components for the establishment and persistence of this invasive monocot. However, controlled studies specifically targeting water relations in M. vimineum are needed. Therefore, the purpose of this study was to determine how different water availabilities influence the growth and physiological performance of M. vimineum. This study utilized experimental microcosms to achieve different water availabilities including low soil moisture (<15% water), moderate soil moisture (ca. 20–30%), and flooded conditions. While both flooded and low soil moisture resulted in diminished growth, M. vimineum still survived under these conditions. Physiological processes including C₄ metabolism, minimum stress under low water conditions, and the ability to increase tissue rigidity may confer some advantages to M. vimineum during periods of limiting water conditions. Similarly, the proportionally low root biomass, shallow root structure, and its ability to maintain stable water relations during flooding and/or soil waterlogging may facilitate M. vimineum’s ability to invade mesic habitats. It is likely, therefore, that the capacity to tolerate both low soil moistures and flooded conditions has enhanced the ability of M. vimineum to populate disturbed systems in central North Carolina.     

A climate for contemporary evolution

A new study of divergence in freshwater fish provides strong evidence of rapid, temperature-mediated adaptation. This study is particularly important in the ongoing debate over the extent and significance of evolutionary response to climate change because divergence has occurred in relatively few generations in spite of ongoing gene flow and in the aftermath of a significant genetic bottleneck, factors that have previously been considered obstacles to evolution. Climate change may thus be more likely to foster contemporary evolutionary responses than has been anticipated, and I argue here for the importance of investigating their possible occurrence.     

Gene dosage studies with pleiotropic mutants of Serratia marcescens superactive in the synthesis of marcescin A and certain other exocellular proteins

Summary Pleiotropic mutants of Serratia marcescens have been isolated. They synthesize greater quantities of the bacteriocin marcescin A and exocellular lipase and exhibit higher rates of spontaneous induction of prophage than does the wild-type strain. These mutants were found to contain more marcescin A plasmid DNA than the parent strain and, furthermore, this increase in plasmid DNA was observed to be proportional to the increase in synthesis of marcescin A. From these results it is proposed that the mutation functions via a gene-dosage effect (at least in the case of bacteriocin synthesis) and causes an elevated synthesis of bacteriocin plasmid DNA.A preliminary report of this work was presented to the 1972 Summer Meeting of the Gesellschaft für Physiologische Chemie held in Bochum, Germany (Timmis and Winkler, 1972).     

Dityrosine is a prominent component of the yeast ascospore wall. A proof of its structure

The yeast ascospore wall consists of four morphologically distinct layers. The hydrophobic surface layers are biogenically derived from the prospore wall and appear dark after OsO4 staining. They seem to be responsible for the stability of the spores against attack by lytic enzymes. By amino acid analysis of acid hydrolysates of ascospore walls, two new peaks were detected, which were shown to be the racemic and meso form, respectively, of dityrosine. The identity of this hitherto unknown component of the yeast ascospore wall with standard dityrosine was proven by 1H NMR and by mass spectrometry. A 13C NMR spectroscopic investigation of the structure of dityrosine confirmed that, in natural dityrosine, the biphenyl linkage is located ortho, ortho to the hydroxyl groups. Following digestion of the inner layers of isolated ascospore walls it was shown that dityrosine is very probably located only in the surface layers. The same conclusion was reached independently by an investigation of spores of a strain homozygous for the mutation gcn1, which lack the outermost layers of the spore wall and were practically devoid of dityrosine. In sporulating yeast, L-tyrosine was readily incorporated into the dityrosine of the ascospore wall. Control experiments involving vegetative a/alpha cells and nonsporulating alpha/alpha cells under sporulation conditions showed that dityrosine is indeed sporulation-specific.     

Deadly liaisons: fatal attraction between CCN matricellular proteins and the tumor necrosis factor family of cytokines

Recent studies have revealed an unexpected synergism between two seemingly unrelated protein families: CCN matricellular proteins and the tumor necrosis factor (TNF) family of cytokines. CCN proteins are dynamically expressed at sites of injury repair and inflammation, where TNF cytokines are also expressed. Although TNFα is an apoptotic inducer in some cancer cells, it activates NFκB to promote survival and proliferation in normal cells, and its cytotoxicity requires inhibition of de novo protein synthesis or NFκB signaling. The presence of CCN1, CCN2, or CCN3 overrides this requirement and unmasks the apoptotic potential of TNFα, thus converting TNFα from a proliferation-promoting protein into an apoptotic inducer. These CCN proteins also enhance the cytotoxicity of other TNF cytokines, including LTα, FasL, and TRAIL. Mechanistically, CCNs function through integrin α₆β₁ and the heparan sulfate proteoglycan (HSPG) syndecan-4 to induce reactive oxygen species (ROS) accumulation, which is essential for apoptotic synergism. Mutant CCN1 proteins defective for binding α₆β₁-HSPGs are unable to induce ROS or apoptotic synergism with TNF cytokines. Further, knockin mice that express an α₆β₁-HSPG-binding defective CCN1 are blunted in TNFα- and Fas-mediated apoptosis, indicating that CCN1 is a physiologic regulator of these processes. These findings implicate CCN proteins as contextual regulators of the inflammatory response by dictating or enhancing the cytotoxicity of TNFα and related cytokines.