scholarly journals In vitro human cell-based TTR-TRβ CALUX assay indicates thyroid hormone transport disruption of short-chain, medium-chain, and long-chain chlorinated paraffins

2021 ◽  
Author(s):  
Jannik Sprengel ◽  
Peter A. Behnisch ◽  
Harrie Besselink ◽  
Abraham Brouwer ◽  
Walter Vetter
Keyword(s):  
Thyroid Hormone ◽  
Structural Similarity ◽  
Short Chain ◽  
Single Chain ◽  
Medium Chain ◽  
Hormone Transport ◽  
Chlorinated Paraffins ◽  
Calux Assay ◽  
Long Chain

AbstractOver the last decades, short-chain chlorinated paraffins (SCCPs), medium-chain chlorinated paraffins (MCCPs), and long-chain chlorinated paraffins (LCCPs) have become the most heavily produced monomeric organohalogen compound class of environmental concern. However, knowledge about their toxicology is still scarce, although SCCPs were shown to have effects on the thyroid hormone system. The lack of data in the case of MCCPs and LCCPs and the structural similarity with perfluoroalkyl substances (PFAS) prompted us to test CPs in the novel TTR-TR CALUX assay for their thyroid hormone transport disrupting potential. Four self-synthesized and additionally purified single chain length CP mixtures (C10-CPs, C11-CPs, C14-CPs and C16-CPs) and two each of industrial MCCP and LCCP products were tested in parallel with PFOA. All CP mixtures influenced the TTR binding of T4, giving activities of 1,300 to 17,000 µg/g PFOA equivalents and lowest observable effect concentrations (LOELs) of 0.95 to 0.029 mM/L incubate. Highest activities and lowest LOELs were observed for C16-CPs (48.3% Cl content, activity 17,000, LOEL 0.047 mM/L) and a LCCP mixture (71.7% Cl content; activity 10,000; LOEL 0.029 mM/L). A trend of higher activities and lower LOELs towards longer chains and higher chlorination degrees was implied, but could not be statistically confirmed. Irrespectively, the less well examined and current-use LCCPs showed the highest response in the TTR-TRβ CALUX assay.

scholarly journals Characterization of Site-Specific Mutations in a Short-Chain-Length/Medium-Chain-Length Polyhydroxyalkanoate Synthase:In VivoandIn VitroStudies of Enzymatic Activity and Substrate Specificity

2013 ◽  
Vol 79 (12) ◽  
pp. 3813-3821 ◽  
Author(s):  
Jo-Ann Chuah ◽  
Satoshi Tomizawa ◽  
Miwa Yamada ◽  
Takeharu Tsuge ◽  
Yoshiharu Doi ◽  
...  
Keyword(s):  
Chain Length ◽  
Fold Increase ◽  
Short Chain ◽  
Pha Synthase ◽  
Wild Type ◽  
Short Chain Length ◽  
Medium Chain ◽  
Medium Chain Length

ABSTRACTSaturation point mutagenesis was carried out at position 479 in the polyhydroxyalkanoate (PHA) synthase fromChromobacteriumsp. strain USM2 (PhaCCs) with specificities for short-chain-length (SCL) [(R)-3-hydroxybutyrate (3HB) and (R)-3-hydroxyvalerate (3HV)] and medium-chain-length (MCL) [(R)-3-hydroxyhexanoate (3HHx)] monomers in an effort to enhance the specificity of the enzyme for 3HHx. A maximum 4-fold increase in 3HHx incorporation and a 1.6-fold increase in PHA biosynthesis, more than the wild-type synthase, was achieved using selected mutant synthases. These increases were subsequently correlated with improved synthase activity and increased preference of PhaCCsfor 3HHx monomers. We found that substitutions with uncharged residues were beneficial, as they resulted in enhanced PHA production and/or 3HHx incorporation. Further analysis led to postulations that the size and geometry of the substrate-binding pocket are determinants of PHA accumulation, 3HHx fraction, and chain length specificity.In vitroactivities for polymerization of 3HV and 3HHx monomers were consistent within vivosubstrate specificities. Ultimately, the preference shown by wild-type and mutant synthases for either SCL (C4and C5) or MCL (C6) substrates substantiates the fundamental classification of PHA synthases.

Encapsulation of pterostilbene in nanoemulsions: influence of lipid composition on physical stability, in vitro digestion, bioaccessibility, and Caco-2 cell monolayer permeability

2019 ◽  
Vol 10 (10) ◽  
pp. 6604-6614 ◽  
Author(s):  
Qianyuan Liu ◽  
Jingjing Chen ◽  
Yang Qin ◽  
Bo Jiang ◽  
Tao Zhang
Keyword(s):  
Lipid Composition ◽  
Cell Monolayer ◽  
Physical Stability ◽  
In Vitro Digestion ◽  
Medium Chain Triglycerides ◽  
Medium Chain ◽  
Monolayer Permeability ◽  
Long Chain Triglycerides ◽  
Long Chain

Nanoemulsions fabricated using medium chain triglycerides as carrier lipid are more effective for delivering pterostilbene than long chain triglycerides.

scholarly journals Rapid inhibition of lipogenesis in vivo in lactating rat mammary gland by medium- or long-chain triacylglycerols and partial reversal by insulin

1980 ◽  
Vol 192 (1) ◽  
pp. 361-364 ◽  
Author(s):  
L Agius ◽  
D H Williamson
Keyword(s):  
Mammary Gland ◽  
Glucose Utilization ◽  
Insulin Administration ◽  
Hepatic Lipogenesis ◽  
Medium Chain ◽  
Rat Mammary Gland ◽  
Long Chain ◽  
Partial Reversal

An intragastric load of medium- or long-chain triacylglycerols inhibited lipogenesis in lactating rat mammary gland in vivo by 82 or 89% respectively. This inhibition was reversed partially by insulin administration. Long-chain triacylglycerols inhibited hepatic lipogenesis in vivo but medium-chain triacylglycerols increased it 2-fold. Glucose utilization in vitro by mammary gland acini from triacylglycerol-fed rat was normal.

Sign in / Sign up

Export Citation Format

Share Document