Periostin Links Mechanical Strain to Inflammation in Abdominal Aortic Aneurysm

Aims

Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammation, which contributes to the pathological remodeling of the extracellular matrix. Although mechanical stress has been suggested to promote inflammation in AAA, the molecular mechanism remains uncertain. Periostin is a matricellular protein known to respond to mechanical strain. The aim of this study was to elucidate the role of periostin in mechanotransduction in the pathogenesis of AAA.

Methods and Results

We found significant increases in periostin protein levels in the walls of human AAA specimens. Tissue localization of periostin was associated with inflammatory cell infiltration and destruction of elastic fibers. We examined whether mechanical strain could stimulate periostin expression in cultured rat vascular smooth muscle cells. Cells subjected to 20% uniaxial cyclic strains showed significant increases in periostin protein expression, focal adhesion kinase (FAK) activation, and secretions of monocyte chemoattractant protein-1 (MCP-1) and the active form of matrix metalloproteinase (MMP)-2. These changes were largely abolished by a periostin-neutralizing antibody and by the FAK inhibitor, PF573228. Interestingly, inhibition of either periostin or FAK caused suppression of the other, indicating a positive feedback loop. In human AAA tissues in ex vivo culture, MCP-1 secretion was dramatically suppressed by PF573228. Moreover, in vivo, periaortic application of recombinant periostin in mice led to FAK activation and MCP-1 upregulation in the aortic walls, which resulted in marked cellular infiltration.

Conclusion

Our findings indicated that periostin plays an important role in mechanotransduction that maintains inflammation via FAK activation in AAA.     

Escherichia coli cytosolic glycerophosphodiester phosphodiesterase (UgpQ) requires Mg2+, Co2+, or Mn2+ for its enzyme activity

Escherichia coli cytosolic glycerophosphodiester phosphodiesterase, UgpQ, functions in the absence of other proteins encoded by the ugp operon and requires Mg²⁺, Mn²⁺, or Co²⁺, in contrast to Ca²⁺-dependent periplasmic glycerophosphodiester phosphodiesterase, GlpQ. UgpQ has broad substrate specificity toward various glycerophosphodiesters, producing sn-glycerol-3-phosphate and the corresponding alcohols. UgpQ accumulates under conditions of phosphate starvation, suggesting that it allows the utilization of glycerophosphodiesters as a source of phosphate. These results clarify how E. coli utilizes glycerophosphodiesters using two homologous enzymes, UgpQ and GlpQ.     

Benefits of mass reduction for commuting flight with heavy food load in Leach’s storm-petrel,Oceanodroma leucorhoa

When rearing chicks, Leach’s storm-petrels (Oceanodroma leucorhoa) commute between foraging areas and breeding colonies with heavy food loads. At this time they should maximize the size of energy-supplying organs in response to increased energy expenditure but minimize total body mass to decrease the energetic cost of flight. Nineteen storm-petrels were killed to examine the changes in body composition and the masses of energy-supplying organs in birds that were incubating and rearing chicks. Parents lost a mean of 7.95 g in body mass between the stages of incubation and chick-rearing mainly via a loss of skin including subcutaneous adipose tissue, and a small fraction of heart and digestive organs, which are considered energy-supplying organs. This mass loss actually enables them to decrease flight cost by 14.4%. The benefits of decreasing flight costs by reducing total body mass are greater than if the energy-supplying organs of birds are enlarged only.

     

Lipase-catalyzed enantioselective esterification of mono-aza-benzo-15-crown-5-ether derivatives in organic media

For the purpose of developing a new chiral crown ether unit as a chiral synthon, three racemic mono azabenzo-15-crown-5-ethers, i.e. (R,S)-1-(6,7,9,10,12,13,15,16-octahydro-5,8,14,17-tetraoxa-11-aza-benzocyclopentadecen-11-yl)-propan-2-ol, (R,S)-2-(6,7,9,10,12,13,15,16-octahydro-5,8,14,17-tetraoxa-11-aza-benzocyclopentadecen-11-yl)-1-phenyl-ethanol and (R , S)-1-[2-(6,7,9,10,12,13,15,16-octahydro-5,8,14,17-tetraoxa-11-aza-benzocyclopentadecen-11-ylmethyl)-phenyl]-ethanol were esterified with vinyl acetate using a lipase from Candida antarctica. The enzymatic acylation of alcohols produced monoacylated products. Two optically active azacrown ethers, (R)-propionic acid 1-methyl-2-(6,7,9,10,12,13,15,16-octahydro-5,8,14,17-tetraoxa-11-aza-benzocyclopentadecen-11-yl)-ethyl ester and (R)-acetic acid 1-[2-(6,7,9,10,12,13,15,16-octahydro-5,8,14,17-tetraoxa-11-aza-benzocyclopentadecen-11-ylmethyl)-phenyl]-ethyl ester were obtained within 48% and 36% yields, respectively and, at an enantiometric excess of over 99% in each case.     

Identification and characterization of 6-dehydroVB-A reductase from Streptomyces antibioticus

Streptomyces antibioticus NF-18 is a hyperproducing strain of a Streptomyces hormone, virginiae butanolide A (VB-A), that induces virginiamycin production of S. virginiae at nanomolar concentrations. To characterize the biosynthetic pathway of VB-A, we identified and characterized for the first time the 6-dehydro VB-A reductase that is responsible for the final reduction step in the biosynthesis. Assay protocols and stabilization conditions were established. The 6-dehydro VB-A reductase was found to require NADPH, not NADH, as a coenzyme. The K(m) values of the enzyme for NADPH and (+/-)-6-dehydro VB-A were determined to be 50 +/- 2 microM and 100 +/- 5 microM, respectively. Ultracentrifugation experiments revealed that 6-dehydro VB-A reductase was present almost exclusively in the 100,000 x g supernatant fraction, indicating that the enzyme is a cytoplasmic-soluble protein. The M(r) of the native 6-dehydro VB-A reductase was estimated to be 82,000 +/- 3000 by molecular sieve HPLC. The optimal pH was found to be 6.7 +/- 0.2.     

Diel changes in resource use and diet overlap in temperate stream fishes

Interspecific variation in diel-scale temporal niches is common in natural communities. Such variation changes population dynamics via effects on the growth and reproduction of individuals. Also at the community level, theory predicts that animals can reduce competition for shared resources by changing diel activity in certain situations. However, the role of diel activity at the community-level has not been examined sufficiently. In this study, to examine whether the diel-scale temporal niche act as a competition-mitigating mechanism for stream fishes at the community level, we surveyed diel changes in microhabitat use and foraging, and the pattern of interspecific diet overlap in the middle reaches of a temperate stream where various fish species that seemed to be either nocturnal or diurnal coexisted. Our results suggest that the fishes forage during both daytime and night, but change their foraging mode at different times of the day, so that the foraging habits of these fish species cannot be divided simply into nocturnal and diurnal. Furthermore, fishes appeared to aggregate in the vicinity of common food resources during time zones with high availability of the resources, and therefore, inter-guild diet overlap was high during certain time zones. On the other hand, when inter-guild diet overlap was low, each fish species used foods or microhabitats that did not any have the potential to be used by species of another guild. Therefore, we conclude that variation in diel niche use is influenced by variation in the fundamental niche and food supply or availability rather than by competitive interaction between fishes in the stream fish community.     

Newly discovered neutral glycosphingolipids in aureobasidin A-resistant zygomycetes: Identification of a novel family of Gala-series glycolipids with core Gal alpha 1-6Gal beta 1-6Gal beta sequences

We found for the first time that Zygomycetes species showed resistance to Aureobasidin A, an antifungal agent. A novel family of neutral glycosphingolipids (GSLs) was found in these fungi and isolated from Mucor hiemalis, which is a typical Zygomycetes species. Their structures were completely determined by compositional sugar, fatty acid, and sphingoid analyses, methylation analysis, matrix-assisted laser desorption ionization time-of-flight/mass spectrometry, and (1)H NMR spectroscopy. They were as follows: Gal beta 1-6Gal beta 1-1Cer (CDS), Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CTS), Gal alpha 1-6Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CTeS), and Gal alpha 1-6Gal alpha 1-6Gal alpha 1-6Gal beta 1-6Gal beta 1-1Cer (CPS). The ceramide moieties of these GSLs consist of 24:0, 25:0, and 26:0 2-hydroxy acids as major fatty acids and 4-hydroxyoctadecasphinganine (phytosphingosine) as the sole sphingoid. However, the glycosylinositolphosphoceramide families that are the major GSLs components in fungi were not detected in Zygomycetes at all. This seems to be the reason that Aureobasidin A is not effective for Zygomycetes as an antifungal agent. Our results indicate that the biosynthetic pathway for GSLs in Zygomycetes is significantly different from those in other fungi and suggest that any inhibitor of this pathway may be effective for mucormycosis, which is a serious pathogenic disease for humans.     

Reduced pain hypersensitivity and inflammation in mice lacking microsomal prostaglandin e synthase-1

We examined the in vivo role of membrane-bound prostaglandin E synthase (mPGES)-1, a terminal enzyme in the PGE2-biosynthetic pathway, using mPGES-1 knockout (KO) mice. Comparison of PGES activity in the membrane fraction of tissues from mPGES-1 KO and wild-type (WT) mice indicated that mPGES-1 accounted for the majority of lipopolysaccharide (LPS)-inducible PGES in WT mice. LPS-stimulated production of PGE2, but not other PGs, was impaired markedly in mPGES-1-null macrophages, although a low level of cyclooxygenase-2-dependent PGE2 production still remained. Pain nociception, as assessed by the acetic acid writhing response, was reduced significantly in KO mice relative to WT mice. This phenotype was particularly evident when these mice were primed with LPS, where the stretching behavior and the peritoneal PGE2 level of KO mice were far less than those of WT mice. Formation of inflammatory granulation tissue and attendant angiogenesis in the dorsum induced by subcutaneous implantation of a cotton thread were reduced significantly in KO mice compared with WT mice. Moreover, collagen antibody-induced arthritis, a model for human rheumatoid arthritis, was milder in KO mice than in WT mice. Collectively, our present results provide unequivocal evidence that mPGES-1 contributes to the formation of PGE2 involved in pain hypersensitivity and inflammation.