heptan-1-ol

ChEBI · EMBL-EBI ↗ · Källdatum saknas · Källans villkor

A primary alcohol that is heptane substituted by a hydroxy group at position 1. It has been isolated from Capillipedium parviflorum.

BugajevViktor; DraberovaLubica; UtekalPavol; BlazikovaMichaela; TumovaMagda; DraberPetr; Sagi-EisenbergRonit · Enhanced Membrane Fluidization and Cholesterol Displacement by 1-Heptanol Inhibit Mast Cell Effector Functions ↗ · Aug 15, 2023 · Källans villkor

Antigen-activated mast cells secrete preformed bioactive compounds from their granules [29]. This process can be quantified by measuring the levels of released mediators, such as histamine or β-glucuronidase [47,53]. Next, we examined the levels of β-glucuronidase in the supernatants of antigen-activated BMMCs exposed to 2.5 mM 1-heptanol for 15 min prior to antigen addition (Figure 6A). In non-activated cells, the amount of β-glucuronidase was similar in the control and 1-heptanol pretreated cells, indicating no change in spontaneous degranulation. This finding supports the notion that short-term exposure of BMMCs to 2.5 mM 1-heptanol is not toxic or activating for mast cells. In the supernatants of antigen-activated control cells, the amount of β-glucuronidase was increased almost ten-fold (29.6 ± 1.6% SEM). In cells treated with 2.5 mM 1-heptanol and activated by antigen, the amount of β-glucuronidase released from the cells was significantly reduced (10.0 ± 0.5% SEM; Figure 6A). The observed inhibition of degranulation by exposure to 2.5 mM 1-heptanol for 15 min was completely reversible, as inferred from the experiments in which washout of 1-heptanol immediately before antigen addition restored degranulation (Figure 6B). These data are consistent with the literature data showing that 1-heptanol-mediated phase separation of membrane molecules is a reversible process [31].

BugajevViktor; DraberovaLubica; UtekalPavol; BlazikovaMichaela; TumovaMagda; DraberPetr; Sagi-EisenbergRonit · Enhanced Membrane Fluidization and Cholesterol Displacement by 1-Heptanol Inhibit Mast Cell Effector Functions ↗ · Aug 15, 2023 · Källans villkor

Mice were bred and maintained in a pathogen-free facility of the Institute of Molecular Genetics, used in compliance with the Institute guidelines and as approved by the Institute Commission for Animal Welfare and Protection (Approval No. 72744021). Precursors of BMMC were isolated from the femurs and tibias of 6-to-8-week-old mice of the C57Bl/6J genotype. BMMCs were cultured for 8 to 12 weeks in a complete growth medium containing 10% (v/v) fetal calf serum (FCS), recombinant mouse IL-3 (15 ng/mL), and recombinant mouse SCF (15 ng/mL). RBL cells, clone 2H3 [43], were grown as an adherent culture [44]. The human embryonic kidney 293FT (HEK293) cell line was provided by the laboratory of Dr. J. Rivera (National Institutes of Health, Bethesda, MD, USA) and cultivated as an adherent culture in Dulbecco’s modified Eagle‘s medium (D6429; Sigma-Aldrich) supplemented with antibiotics (100 U/mL penicillin, 100 μg/mL streptomycin), 10% FCS (Biosera, Cholet, France; catalog no. FB-1090/500), and 2.5 mM L-glutamine. Human c-KIT-positive mast cell line ROSA was a kind gift of Dr. Michel Arock (Laboratoire d’Hématologie Biologique, Hôpital Pitié-Salpêtrière, Paris, France). ROSA cells were grown as a floating culture as described in [45].

BugajevViktor; DraberovaLubica; UtekalPavol; BlazikovaMichaela; TumovaMagda; DraberPetr; Sagi-EisenbergRonit · Enhanced Membrane Fluidization and Cholesterol Displacement by 1-Heptanol Inhibit Mast Cell Effector Functions ↗ · Aug 15, 2023 · Källans villkor

This study shows that 1-heptanol increases membrane fluidity, as measured by FRAP, of FITC-IgE-labeled FcεRI complexes and ORAI1-mCherry. Increased lateral mobility of FcεRI and reduced FceRI internalization due to 1-heptanol do not interfere with the initial steps in antigen-activated mast cells, as reflected by enhanced phosphorylation of proteins of early signaling events, including FcεRI-β chain, SYK, LAT1, and PLCγ1. Nevertheless, calcium response, degranulation, ROS production, and TNF-α levels were impaired in 1-heptanol-treated and FcεRI-activated cells. Further analysis showed that 1-heptanol-mediated membrane hyperfluidization altered the dynamics of STIM1-ORAI1 coupling in resting and activated cells, as determined by flow-FRET, resulting in reduced calcium uptake. These events may be associated with the enhanced lateral mobility of ORAI1. Membrane hyperfluidization mediated by 1-heptanol enhanced the sensitivity of cells to increased temperature and resulted in enhanced production of HSP70, which could contribute to the inhibition of cytokine expression. These findings are summarized in Figure 12. The combined data prove that 1-heptanol inhibits mast cell effector functions; this should be considered when 1-heptanol is used in the food and fragrance industries.