Deletion of metallothionein exacerbates intermittent hypoxia-induced oxidative and inflammatory injury in aorta.

Abstract

The present study was to explore the effect of metallothionein (MT) on intermittent hypoxia (IH) induced aortic pathogenic changes. Markers of oxidative damages, inflammation, and vascular remodeling were observed by immunohistochemical staining after 3 days and 1, 3, and 8 weeks after IH exposures. Endogenous MT was induced after 3 days of IH but was significantly decreased after 8 weeks of IH. Compared with the wild-type mice, MT knock-out mice exhibited earlier and more severe pathogenic changes of oxidative damages, inflammatory responses, and cellular apoptosis, as indicated by the significant accumulation of collagen, increased levels of connective tissue growth factor, transforming growth factor β1, tumor necrosis factor-alpha, vascular cell adhesion molecule 1,3-nitrotyrosine, and 4-hydroxy-2-nonenal in the aorta. These findings suggested that chronic IH may lead to aortic damages characterized by oxidative stress and inflammation, and MT may play a pivotal role in the above pathogenesis process.

• Authors: Shanshan Zhou, Yonggang Wang, Yi Tan, Xiaohong Cai, Lu Cai, Jun Cai, Yang Zheng
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2014 Pg. 141053 ( 2014) ISSN: 1942-0994 [Electronic] United States
• PMID: 25177426 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aldehydes
• CCN2 protein, mouse
• Tumor Necrosis Factor-alpha
• Connective Tissue Growth Factor
• 3-nitrotyrosine
• Tyrosine
• Metallothionein
• Nitric Oxide Synthase Type III
• Nos3 protein, mouse
• NADPH Oxidases
• neutrophil cytosolic factor 1
• 4-hydroxy-2-nonenal

Topics

• Aldehydes (metabolism)
• Animals
• Aorta (injuries, metabolism, pathology)
• Apoptosis
• Connective Tissue Growth Factor (genetics, metabolism)
• Hypoxia
• Metallothionein (deficiency, genetics)
• Mice
• Mice, Knockout
• NADPH Oxidases (metabolism)
• Nitric Oxide Synthase Type III (metabolism)
• Oxidative Stress
• Time Factors
• Tumor Necrosis Factor-alpha (genetics, metabolism)
• Tyrosine (analogs & derivatives, metabolism)