scholarly journals Effect of lipopolysaccharide (LPS) on HAEC cells. Does nicotinamide N-methyltranferase sensitize HAEC cells to LPS?

2021 ◽  
Author(s):  
Oksana Stepinska ◽  
Dorota Dymkowska ◽  
Lukasz Mateuszuk ◽  
Krzysztof Olaf Zablocki

Treatment of endothelial cells with bacterial lipopolysaccharide (LPS) evokes a number of metabolic and functional consequences which built a multifaceted physiological response of endothelium to bacterial infection. Here effects of LPS on human aortic endothelial cells (HAEC) have been investigated. Among the spectrum of biochemical changes substantially elevated N-nicotinamide methyltransferase (NNMT) protein level was particularly intriguing. It has been shown that silencing of the NNMT-encoding gene prevented several changes which are observed in control HAECs due to treatment with LPS. They include significantly increased cytosolic Ca2+ concentration and abnormally strong calcium response to thapsigargin, altered energy metabolism which is switched to anaerobic glycolysis and rearrangement of the mitochondrial network organization. Biochemical mechanisms behind protecting effect of partial NNMT deficiency remains unknown but we speculate that the primary role in this phenomenon is attributed to normalized Ca2+ response in cells partially deprived of the NNMT gene. However, this assumption needs to be verified experimentally. Nevertheless, this paper focuses the reader attention on NNMT, which is an important enzyme that potentially may affect cellular metabolism by two means: direct influence based on a regulation of NAD+ synthesis through modulation of nicotinamide availability, and a regulation of S-adenosylmethionine concentration and therefore controlling of methylation processes including modification of chromatin and epigenetic effects

2014 ◽  
Vol 103 (suppl 1) ◽  
pp. S142.1-S142
Author(s):  
A Oberbach ◽  
V Adams ◽  
N Schlichting ◽  
N Jehmich ◽  
U Voelker ◽  
...  

2005 ◽  
Vol 73 (12) ◽  
pp. 8050-8059 ◽  
Author(s):  
Hiromichi Yumoto ◽  
Hsin-Hua Chou ◽  
Yusuke Takahashi ◽  
Michael Davey ◽  
Frank C. Gibson ◽  
...  

ABSTRACT Toll-like receptors (TLRs) are differentially up-regulated in response to microbial infection and chronic inflammatory diseases such as atherosclerosis. Epidemiological data support the idea that periodontal disease may be a risk factor for acceleration of atherosclerosis. Porphyromonas gingivalis, the etiological agent of periodontal disease, invades endothelium, has been detected in human atheromatous tissue, and accelerates atheroma formation in apolipoprotein E−/− mice with concurrent induction of TLRs in the aorta. As endothelial cells can present antigen via TLRs and play an important role in the development of atherosclerosis, we examined TLR expression in human aortic endothelial cells (HAEC) cultured with wild-type P. gingivalis, a fimbria-deficient mutant, and purified antigens. We observed increased TLR expression in HAEC infected with wild-type P. gingivalis by fluorescence-activated cell sorter, but not with noninvasive, fimbria-deficient mutant or purified P. gingivalis antigens. Following a wild-type P. gingivalis challenge, functional TLR2 and TLR4 activation was assessed by subsequent stimulation with TLR agonists Staphylococcus aureus lipoteichoic acid (SLTA; TLR2 ligand) and Escherichia coli lipopolysaccharide (LPS; TLR4 ligand). Unchallenged HAEC failed to elicit monocyte chemoattractant protein 1 (MCP-1) in response to LPS or SLTA but did so when cultured with wild-type P. gingivalis. P. gingivalis-induced TLR2 and -4 expression on HAEC functionally reacted to SLTA and E. coli LPS as measured by a further increase in MCP-1 production. Furthermore, MCP-1 expression elicited by E. coli LPS was inhibitable with TLR4-specific antibody and polymyxin B. These results indicate that invasive P. gingivalis stimulates TLR expression on the surface of endothelium and these primed cells respond to defined TLR-specific ligands.


PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252816
Author(s):  
Lei Chen ◽  
Rachel Holder ◽  
Charles Porter ◽  
Zubair Shah

The toxicity of doxorubicin to the cardiovascular system often limits its benefits and widespread use as chemotherapy. The mechanisms involved in doxorubicin-induced cardiovascular damage and possible protective interventions are not well-explored. Using human aortic endothelial cells, we show vitamin D3 strongly attenuates doxorubicin-induced senescence and cell cycle arrest. We further show the protective effects of vitamin D3 are mediated by the upregulation of IL-10 and FOXO3a expression through fine modulation of pAMPKα/SIRT1/FOXO3a complex activity. These results have great significance in finding a target for mitigating doxorubicin-induced cardiovascular toxicity.


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