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Morin C.,Universite de Sherbrooke | Fortin S.,Marine Biotechnology Research Center | Cantin A.M.,Universite de Sherbrooke | Rousseau E.,Universite de Sherbrooke
American Journal of Respiratory Cell and Molecular Biology | Year: 2011

The effects of a newly synthesized docosahexaenoic acid (DHA) derivative, CRBM-0244, on lung inflammation and airway hyperresponsiveness were determined in an in vitro model of TNF-α-stimulatedhuman bronchi and in an in vivo model of allergic asthma. Mechanical tension measurements revealed that CRBM-0244 prevented bronchial hyperresponsiveness in TNF-α-pretreated human bronchi.Moreover, treatmentwithCRBM-0244 resultedin a decrease in NF-κB activation and cyclooxygenase-2 (COX-2) overexpression triggered by TNF-α. The inhibition of peroxisome proliferator-activated receptor-γ with GW9662 abolished the CRBM-0244-mediated anti-inflammatory effects. CRBM-0244 reduced the Ca2+ sensitivity of bronchial smooth muscle through a decrease in the phosphorylation and expression of the PKC-potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17 kDa (CPI-17). Results also revealed an overexpression of CPI-17 protein in lung biopsies derived from patients with asthma. Furthermore, the presence of specialized enzymes such as 5-lipoxygenase and 15- lipoxygenase in the lung may convert CRBM-0244 into active mediators, leading to the resolution of inflammation. The in vivo anti-inflammatory properties of CRBM-0244 were also investigated in a guinea pig model of allergic asthma. After oral administration of CRBM-0244, airway leukocyte recruitment, airwaymucus, ovalbuminspecific IgE, and proinflammatory markers such as TNF-α and COX-2 were markedly reduced. Hence, CRBM-0244 treatment prevents airway hyperresponsiveness, Ca2+ hypersensitivity, and the overexpression of CPI-17 in lung tissue. Together, these findings provide key evidence regarding the mode of action of CRBM-0244 in the lung, and point to new therapeutic strategies for modulating inflammation in patients with asthma. Source

Liu A.,Shandong University | Liu A.,Marine Biotechnology Research Center | Mi Z.-H.,Shandong University | Mi Z.-H.,Marine Biotechnology Research Center | And 16 more authors.
Frontiers in Microbiology | Year: 2016

Most marine bacteria secrete exopolysaccharide (EPS), which is important for bacterial survival in the marine environment. However, it is still unclear whether the self-secreted EPS is involved in marine bacterial motility. Here we studied the role of EPS in the lateral flagella-driven swarming motility of benthic bacterium Pseudoalteromonas sp. SM9913 (SM9913) by a comparison of wild SM9913 and ΔepsT, an EPS synthesis defective mutant. Reduction of EPS production in ΔepsT did not affect the growth rate or the swimming motility, but significantly decreased the swarming motility on a swarming plate, suggesting that the EPS may play a role in SM9913 swarming. However, the expression and assembly of lateral flagella in ΔepsT were not affected. Instead, ΔepsT had a different swarming behavior from wild SM9913. The swarming of ΔepsT did not have an obvious rapid swarming period, and its rate became much lower than that of wild SM9913 after 35 h incubation. An addition of surfactin or SM9913 EPS on the surface of the swarming plate could rescue the swarming level. These results indicate that the self-secreted EPS is required for the swarming of SM9913. This study widens our understanding of the function of the EPS of benthic bacteria. © 2016 Liu, Mi, Zheng, Yu, Su, Chen, Xie, Zhou, Zhang and Qin. Source

Ran L.-Y.,Shandong University | Ran L.-Y.,Marine Biotechnology Research Center | Su H.-N.,Shandong University | Su H.-N.,Marine Biotechnology Research Center | And 21 more authors.
Journal of Biological Chemistry | Year: 2014

Collagen is an insoluble protein that widely distributes in the extracellular matrix of marine animals. Collagen degradation is an important step in the marine nitrogen cycle. However, the mechanism of marine collagen degradation is still largely unknown. Here, a novel subtilisin-like collagenolytic protease, myroicolsin, which is secreted by the deep sea bacterium Myroides profundi D25, was purified and characterized, and its collagenolytic mechanism was studied. Myroicolsin displays low identity (<30%) to previously characterized subtilisin-like proteases, and it contains a novel domain structure. Protein truncation indicated that the Pro secretion system C-terminal sorting domain in the precursor protein is involved in the cleavage of the N-propeptide, and the linker is required for protein folding during myroicolsin maturation. The C-terminal β-jelly roll domain did not bind insoluble collagen fiber, suggesting that myroicolsin may degrade collagen without the assistance of a collagen-binding domain. Myroicolsin had broad specificity for various collagens, especially fish-insoluble collagen. The favored residue at the P1 site was basic arginine. Scanning electron microscopy and atomic force microscopy, together with biochemical analyses, confirmed that collagen fiber degradation by myroicolsin begins with the hydrolysis of proteoglycans and telopeptides in collagen fibers and fibrils. Myroicolsin showed strikingly different cleavage patterns between native and denatured collagens. A collagen degradation model of myroicolsin was proposed based on our results. Our study provides molecular insight into the collagen degradation mechanism and structural characterization of a subtilisin-like collagenolytic protease secreted by a deep sea bacterium, shedding light on the degradation mechanism of deep sea sedimentary organic nitrogen. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Source

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