We examined the ability of Aeromonas hydrophila to lyse elastin. Eight of 13 strains showed elastolytic activity on agar medium containing elastin and 5 strains did not. In order to examine the involvement of the metalloprotease of A. hydrophila (AMP) in elastolytic activity, we made the amp-deletion mutant strain from an elastolytic strain. The elastolytic activity of the strain decreased with this deletion. The analysis of AMP released into the culture supernatant showed that AMP appeared outside of the cell as the intermediate consisting of a mature domain and carboxy terminal (C-terminal) propeptide domain. Further analysis showed that the intermediate has the ability to lyse elastin and that loss of the C-terminal domain causes loss of the elastolytic activity of the intermediate. We then determined the nucleotide sequence of the amps of all strains used in this study. Phylogenetic analysis revealed that these AMPs were divided into three groups. The AMPs from elastolytic strains belong to group I or group II, and AMPs from non-elastolytic strains belong to group III. The distance between group I and group II is small, but group III is located separately from groups I and II. Comparison of the amino acid residues of the C-terminal domain revealed that there are 13 amino acid residues specific to the C-terminal domain of group III. This indicates that the conformation of the C-terminal propeptide domain formed by these specific amino acid residues is important for AMP to express elastolytic activity.
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http://dx.doi.org/10.1248/bpb.b13-00161 | DOI Listing |
Microbiol Spectr
October 2024
Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
Am J Physiol Lung Cell Mol Physiol
November 2024
Center for Lung Biology, University of Washington, Seattle, Washington, United States.
Chronic obstructive pulmonary disease (COPD), comprised of chronic bronchitis and emphysema, is a leading cause of morbidity and mortality worldwide. Mitogen-activated protein 2 kinase (MAP2K) pathway activation is present in COPD lung tissue and a genetic polymorphism in associates with FEV1 decline in COPD, suggesting it may contribute to disease pathogenesis. To test the functional contribution of in cigarette smoke (CS)-induced lung inflammation, we used a short-term CS exposure model in mice deficient in myeloid () and wild-type mice ().
View Article and Find Full Text PDFJ Biomed Mater Res A
April 2024
Department of Bioengineering, Lehigh University, Bethlehem, Pennsylvania, USA.
The over-expression of c-Jun N-terminal kinase (JNK2), a stress activated mitogen kinase, in the aortic wall plays a critical role in the formation and progression of abdominal aortic aneurysm (AAA). This triggers chronic downstream upregulation of elastolytic matrix metalloproteinases (MMPs), MMPs2 and 9 to cause progressive proteolytic breakdown of the wall elastic matrix. We have previously shown that siNRA knockdown of JNK2 gene expression in an AAA culture model stimulates downstream elastin gene expression, elastic fiber formation, crosslinking and reduces elastolytic MMPs2 and 9.
View Article and Find Full Text PDFTissue Eng Part A
January 2024
Department of Bioengineering, Lehigh University, Bethlehem, Pennsylvania, USA.
Abdominal aortic aneurysm (AAA) is a critical, multifactorial cardiovascular disorder marked by localized dilatation of the abdominal aorta. A major challenge to countering the pathophysiology of AAAs lies in the naturally irreversible breakdown of elastic fibers in the aorta wall, which is linked to the poor elastogenicity of adult and diseased vascular smooth muscle cells (SMCs) and their impaired ability to assemble mature elastic fibers in a chronic proteolytic tissue milieu. We have previously shown that these are downstream effects of neutrophil elastase-induced activation of the epidermal growth factor receptor (EGFR) activity in aneurysmal SMCs.
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