Biochemical and biophysical research communications
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Biochem. Biophys. Res. Commun. · Apr 2012
Sirtuin inhibition attenuates the production of inflammatory cytokines in lipopolysaccharide-stimulated macrophages.
In several inflammatory conditions such as rheumatoid arthritis or sepsis, the regulatory mechanisms of inflammation are inefficient and the excessive inflammatory response leads to damage to the host. Sirtuins are class III histone deacetylases that modulate the activity of several transcription factors that are implicated in immune responses. ⋯ The reduction of cytokine production was associated with decreased nuclear factor kappa B (NF-κB) activity and inhibitor kappa B alpha (IκBα) phosphorylation while no impact was observed on the phosphorylation status of p38 mitogen-activated kinase (p38 MAPK). This work shows that sirtuin pharmacologic inhibitors are a promising tool for the treatment of inflammatory conditions.
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Biochem. Biophys. Res. Commun. · Apr 2012
Activation of the Wnt/β-catenin signaling pathway is associated with glial proliferation in the adult spinal cord of ALS transgenic mice.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive and fatal loss of motor neurons. In ALS, there is a significant cell proliferation in response to neurodegeneration; however, the exact molecular mechanisms of cell proliferation and differentiation are unclear. The Wnt signaling pathway has been shown to be involved in neurodegenerative processes. ⋯ Moreover, BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. Our findings suggest that neurodegeneration activates the Wnt/β-catenin signaling pathway, which is associated with glial proliferation in the adult spinal cord of ALS transgenic mice. This mechanism may be significant in clinical gene therapy.
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Biochem. Biophys. Res. Commun. · Mar 2012
Tie1 regulates the Tie2 agonistic role of angiopoietin-2 in human lymphatic endothelial cells.
Although Angiopoietin (Ang) 2 has been shown to function as a Tie2 antagonist in vascular endothelial cells, several recent studies on Ang2-deficient mice have reported that, like Ang1, Ang2 acts as a Tie2 agonist during in vivo lymphangiogenesis. However, the mechanism governing the Tie2 agonistic activity of Ang2 in lymphatic endothelial cells has not been investigated. We found that both Ang1 and Ang2 enhanced the in vitro angiogenic and anti-apoptotic activities of human lymphatic endothelial cells (HLECs) through the Tie2/Akt signaling pathway, while only Ang1 elicited such effects in human umbilical vein vascular endothelial cells (HUVECs). ⋯ This inhibitory role of Tie1 in Ang2-induced Tie2 activation was also confirmed in non-endothelial cells with adenovirus-mediated ectopic expression of Tie1 and/or Tie2. To our knowledge, this study is the first to describe how Ang2 acts as a Tie2 agonist in HLECs. Our results suggest that the expression level of Tie1 and its physical interaction with Tie2 defines whether Ang2 functions as a Tie2 agonist or antagonist, thereby determining the context-dependent differential endothelial sensitivity to Ang2.
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Biochem. Biophys. Res. Commun. · Feb 2012
Replacement of microglial cells using Clodronate liposome and bone marrow transplantation in the central nervous system of SOD1(G93A) transgenic mice as an in vivo model of amyotrophic lateral sclerosis.
Disease progression of amyotrophic lateral sclerosis (ALS) is partially mediated by the toxic microenvironment established by microglia. In the present study, we used SOD1G93A transgenic mice as an in vivo ALS model and replaced microglia expressing mutant SOD1 (mSOD1) with microglia expressing wild-type SOD1 (w/tSOD1) to modulate the toxic microenvironment. Stereotactic injection of Clodronate liposome, a selective toxin against the monocyte/macrophage system, into the fourth ventricle of the brains of 12-week-old asymptomatic ALS mice reduced the number of microglia effectively in the central nervous system. ⋯ The replacement of microglia significantly slowed disease progression and prolonged survival of the ALS mice compared with the ALS mice treated by stereotactic injection of PBS-liposome and BMT with BMCs expressing mSOD1 or w/tSOD1. These results suggest that replacement of microglia would improve the neural cell microenvironment, thereby slowing disease progression. The mechanisms and functional implications of this replacement require further elucidation.
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Biochem. Biophys. Res. Commun. · Jan 2012
Mesenchymal stem cell isolation and characterization from human spinal ligaments.
Mesenchymal stem cells (MSCs) have a fibroblast-like morphology, multilineage potential, long-term viability and capacity for self-renewal. While several articles describe isolating MSCs from various human tissues, there are no reports of isolating MSCs from human spinal ligaments, and their localization in situ. If MSCs are found in human spinal ligaments, they could be used to investigate hypertrophy or ossification of spinal ligaments. ⋯ Immunohistochemistry revealed the localization of CD90-positive cells in the collagenous matrix of the ligament, and in adjacent small blood vessels. We isolated and expanded MSCs from human spinal ligaments and demonstrated localization of MSCs in spinal ligaments. These cells may play an indispensable role in elucidating the pathogenesis of numerous spinal diseases.