scholarly journals Small Chain Fatty Acid Phenylbutyric Acid Alleviated Inflammation-Induced Endoplasmic Reticulum Stress in Endothelial Cells

2021 ◽  
Author(s):  
Oski Illiandri

Endothelial cells (EC) have dynamic properties and high plasticity in response to microenvironmental change. A proinflammatory cytokine such as tumor necrotizing factor-α (TNF-α) can induce EC phenotype shift to osteoinduction properties by releasing a potent osteogenic cytokine, namely bone morphogenetic protein 2 (BMP2). Normally BMP2 acts as an osteoblast stimulating factor in bone and cartilage tissue. BMP2 activation in vascular tissue will invite osteoblast recruitment and mineralization and generated pathological vascular stiffening and calcification. Recently, endoplasmic reticulum stress (ERS) has been emerging as a new target therapy in many vascular diseases such as vascular stiffening and calcification. Some short-chain fatty acid like 4-phenyl butyric acid has been shown had anti-ERS properties. However, the role of 4-phenyl butyric acid in BMP2 inhibition in endothelial cells is still poorly understood. Hence, we investigated the role of 4-phenyl butyric acid in inflammation-induced BMP2 expression in human vein derived endothelial cells. Endothelial cells obtained from a baby born umbilical vein were cultured and pre-treated with TNF-α (5 ng/ml) as inflammation precondition. Multiple doses of 4-phenyl butyrate acid (4- PBA) 1 nM/mL, 2 nM/mL, and 3 nM/m were used as ERS inhibitors. The expression of two ERS biomarkers, glucose-related protein-8 (GRP78) and activating transcription factor-6 (ATF6), were measured. Statistical analysis was done using one-way ANOVA and Kruskal Wallis tests, and P<0.01 considered as significant. 4- PBA decrease luminal BMP2 at dose one nM/L, GRP78 at dose 1 nM/L, and translocated ATF6 expression at dose 1 nM/L in endothelial culture dose-dependently. Short-chain fatty acid 4-phenylbutyrate acid decreases luminal ERS marker GRP78 and translocated ATF6 expression in endothelial culture. ERS has a role in osteoinductive phenotype shifting in inflammation endothelial cells, which was the novelty of this research. Further research needs to elucidate ERS inhibition in in vivo experiment.

2021 ◽  
Author(s):  
Shahnaz Haque

Enterohemorrhagic Escherichia coli (EHEC) 0157:H7 is a food-borne pathogen that causes hemolytic uremic syndrome and hemorrhagic colitis. The mechanisms underlying the adhesion of EHEC 0157:H7 to intestinal epithelial cells are not well understood. Like other food-borne pathogens, ECEC 0157:H7 must survive the acid stress of the gastric juice in the stomach and short chain fatty acid in the intestine in order to colonize the large intestine. We have found that acid stress and short chain fatty acid stress significantly enhance host-adhesion of EHEC 0157:H7 and also upregulates expression of EHEC fimbrial genes, lpfA1, lpfA2 and yagZ, as demonstrated by our DNA microarray. We now report that disruption of the yagZ (also known as the E. coli common pilus A) gene results in loss of the acid-induced and short chain fatty acid-induced adhesion increase seen for the wild type strain. When the yagZ mutant is complemented with yagZ, the sress-induced and short chain fatty acid-induced adhesion increase seen for the wild type strain. When the yagZ mutant is complemented with yagZ, the stress-induced adhesion pehnotype is restored, confirming the role of yagZ in the acid as well as short chain fatty acid induced adhesion to HEp-2 cells. On the other hand, neither disruption in the long polar fimbria genes lpfA1 or lpfA2 in the wild type showed any effect in adherence to HEp-2 cells; rather displaying a hyperadherant phenotype to HEp-2 cells after acid-induced or short chain fatty acid-induced stress. The results also indicate that acid or short chain fatty acid stress, which is a part of the host's natural defense mechanism against pathogens, may regulate virulence factors resulting in enhanced bacteria-host attachment during colonization in the human or bovine host.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kristen Lednovich ◽  
Medha Priyadarshini ◽  
Kumar Kotlo ◽  
Kai Xu ◽  
Shubha Priyamvada ◽  
...  

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 79-79
Author(s):  
Jae-Cheol Jang ◽  
Aqsa Javaid ◽  
Pedro E Urriola ◽  
Gerald C Shurson

Abstract An experiment was conducted to investigate the effect of exogenous enzyme supplementation and solid-state fermentation (SSF) with a mixed bacterial culture on in vitro dry matter digestibility (IVDMD) and short chain fatty acid (SCFA) production of soybean meal (SBM) or rapeseed meal (RSM). A 2 × 2 factorial design was used and included the factors of 1) exogenous enzyme cocktail (supplemented and non-supplemented), 2) microbial fermentation (fermented and non-fermented) applied to SBM or RSM in vitro. The exogenous enzyme cocktail consisted of non-starch polysaccharide (NSP) degrading enzymes (NSP-EZ) with phytase (10,000 FTU/kg), and the SSF were carried out using Bacillus subtilis. The fermented feed ingredients were collected after 48 h incubation at 37oC. Samples were hydrolyzed in two steps using pepsin and pancreatin to calculate IVDMD. Subsequently, the hydrolyzed residues were filtered, dried, and pooled for incubation in a buffered mineral solution with fresh swine feces. Gas production kinetics during fermentation was measured for 72 h and analyzed by fitting data to an exponential model. The fermentation residues were filtered, and the supernatant was analyzed for concentration of SCFA. The IVDMD from simulated gastric and small intestinal hydrolysis was greater (P &lt; 0.01) for SSF in both SBM and RSM. During fermentation, the hydrolysis residue from SBM treated with SSF required less time to reach half asymptote, had greater maximal gas production, and greater fractional degradation (P &lt; 0.01, respectively) compared with non-fermented SBM. The IVDMD from simulated total tract digestion was greater (P &lt; 0.01) for SSF in RSM compared with SBM, while SBM had greater IVDMD for both SSF and NSP-EZ (P &lt; 0.01). Production of butyric acid was greater for SSF (P &lt; 0.01) compared with non-SSF in both SBM and RSM. These results suggest that SSF can improve IVDMD and produce greater amounts of butyric acid compared with NSP-EZ supplementation in SBM and RSM.


2018 ◽  
pp. 1091-1115 ◽  
Author(s):  
Medha Priyadarshini ◽  
Kumar U. Kotlo ◽  
Pradeep K. Dudeja ◽  
Brian T. Layden

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Linlin Li ◽  
Yinan Hua ◽  
Jun Ren

Background and Aims. Dysregulation of Akt has been implicated in diseases such as cancer and diabetes, although little is known about the role of Akt deficiency on cardiomyocyte contractile function. This study was designed to examine the effect of Akt2 knockout-induced cardiomyocyte contractile response and the effect of dietary supplementation of short-chain fatty acid propionate on Akt2 knockout-induced cardiac dysfunction, if any.Methods and Results. Adult male wild-type (WT) and Akt2 knockout mice were treated with propionate (0.3 g/kg, p.o.) or vehicle for 7 days. Oral glucose tolerance test (OGTT) was performed. Cardiomyocyte contractile function and mitochondrial membrane potential were assessed. Expression of insulin-signaling molecules Akt, PTEN, GSK3β, and eNOS receptors for short-chain fatty acids GPR41, and GPR43 as well as protein phosphatase PP2AA, PP2AB, PP2C were evaluated using Western blot analysis. Our results revealed that Akt2 knockout led to overt glucose intolerance, compromised cardiomyocyte contractile function (reduced peak shortening and maximal velocity of shortening/relengthening as well as prolonged relengthening), loss of mitochondrial membrane potential, decreased GPR41 and elevated GPR43 expression, all of which, with the exception of glucose intolerance and elevated GPR43 level, were significantly attenuated by propionate. Neither Akt2 knockout nor propionate affected the expression of protein phosphatases, eNOS, pan, and phosphorylated PTEN and GSK3β.Conclusions. Taken together, these data depicted that Akt2 knockout may elicit cardiomyocyte contractile and mitochondrial defects and a beneficial role of propionate or short-chain fatty acids against Akt2 deficiency-induced cardiac anomalies.


2019 ◽  
Vol 20 (18) ◽  
pp. 4477 ◽  
Author(s):  
Sunita Keshari ◽  
Arun Balasubramaniam ◽  
Binderiya Myagmardoloonjin ◽  
Deron Raymond Herr ◽  
Indira Putri Negari ◽  
...  

The glycerol fermentation of probiotic Staphylococcus epidermidis (S. epidermidis) in the skin microbiome produced butyric acid in vitro at concentrations in the millimolar range. The exposure of dorsal skin of mice to ultraviolet B (UVB) light provoked a significant increased production of pro-inflammatory interleukin (IL)-6 cytokine. Topical application of butyric acid alone or S. epidermidis with glycerol remarkably ameliorated the UVB-induced IL-6 production. In vivo knockdown of short-chain fatty acid receptor 2 (FFAR2) in mouse skin considerably blocked the probiotic effect of S. epidermidis on suppression of UVB-induced IL-6 production. These results demonstrate that butyric acid in the metabolites of fermenting skin probiotic bacteria mediates FFAR2 to modulate the production of pro-inflammatory cytokines induced by UVB.


2021 ◽  
Vol 12 (7) ◽  
pp. 2886-2900
Author(s):  
Yetong Xu ◽  
Anne Katrine Bolvig ◽  
Brendan McCarthy-Sinclair ◽  
Maria L. Marco ◽  
Knud Erik Bach Knudsen ◽  
...  

Rye bran diet induced different DF degradation processes and SCFA profile compared with refined wheat cellulose, while antibiotics had marginal effects on digestibility and DF degradation but hampered butyrate production.


Sign in / Sign up

Export Citation Format

Share Document