Maintenance of endoplasmic reticulum (ER) function is achieved in part through Ire1 (inositol-requiring enzyme 1), a transmembrane protein activated by protein misfolding in the ER. The cytoplasmic nuclease domain of Ire1 cleaves the messenger RNA (mRNA) encoding XBP-1 (X-box–binding protein 1), enabling splicing and production of this active transcription factor. We recently showed that Ire1 activation independently induces the rapid turnover of mRNAs encoding membrane and secreted proteins in Drosophila melanogaster cells through a pathway we call regulated Ire1-dependent decay (RIDD). In this study, we show that mouse fibroblasts expressing wild-type Ire1 but not an Ire1 variant lacking nuclease activity also degrade mRNAs in response to ER stress. Using a second variant of Ire1 that is activated by a small adenosine triphosphate analogue, we show that although XBP-1 splicing can be artificially induced in the absence of ER stress, RIDD appears to require both Ire1 activity and ER stress. Our data suggest that cells use a multitiered mechanism by which different conditions in the ER lead to distinct outputs from Ire1.
Endoplasmic reticulum (ER) stress induces an mRNA decay pathway termed regulated Ire-dependent decay (RIDD). This study shows that in Drosophila cells, ER association is sufficient for targeting mRNAs to RIDD and most membrane-associated mRNAs are degraded more rapidly during ER stress. It is also reported that a small number of mRNAs are specifically protected from this default pathway.
Research on the biological effects of essential oils on human skin cells is scarce. In the current study, we primarily explored the biological activities of 10 essential oils (nine single and one blend) in a pre-inflamed human dermal fibroblast system that simulated chronic inflammation. We measured levels of proteins critical for inflammation, immune responses, and tissue-remodeling processes. The nine single oils were distilled from Citrus bergamia (bergamot), Coriandrum sativum (cilantro), Pelargonium graveolens (geranium), Helichrysum italicum (helichrysum), Pogostemon cablin (patchouli), Citrus aurantium (petitgrain), Santalum album (sandalwood), Nardostachys jatamansi (spikenard), and Cananga odorata (ylang ylang). The essential oil blend (commercial name Immortelle) is composed of oils from frankincense, Hawaiian sandalwood, lavender, myrrh, helichrysum, and rose. All the studied oils were significantly anti-proliferative against these cells. Furthermore, bergamot, cilantro, and spikenard essential oils primarily inhibited protein molecules related to inflammation, immune responses, and tissue-remodeling processes, suggesting they have anti-inflammatory and wound healing properties. Helichrysum and ylang ylang essential oils, as well as Immortelle primarily inhibited tissue remodeling-related proteins, suggesting a wound healing property. The data are consistent with the results of existing studies examining these oils in other models and suggest that the studied oils may be promising therapeutic candidates. Further research into their biological mechanisms of action is recommended. The differential effects of these essential oils suggest that they exert activities by different mechanisms or pathways, warranting further investigation. The chemical composition of these oils was analyzed using gas chromatography–mass spectrometry.
Cinnamon has been used as a flavoring and medicinal agent for centuries. Much research has focused on cinnamon bark powder, which contains antioxidants, flavonoids, carotenoids, vitamins, minerals, fiber, and small amounts of essential oil. However, isolated and concentrated cinnamon essential oil may also have important medicinal qualities, particularly in antidiabetic therapy. Some of the most common essential oil constituents identified in the literature include cinnamaldehyde, eugenol, and beta-caryophyllene. Due to their high concentration in cinnamon essential oil, these constituents are hypothesized to have the most significant physiological activity. Here, we present a brief review of literature on cinnamon oil and its constituents as they relate to glucose metabolism and diabetic pathogenesis. We also present molecular docking simulations of these cinnamon essential oil constituents (cinnamaldehyde, eugenol, beta-caryophyllene) that suggest interaction with several key enzymes in glucometabolic pathways.
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