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Protein translation associated to PERK arm is a new target for regulation of metainflammation: A connection with hepatocyte cholesterol.

A new interesting article has been published in J Cell Biochem. 2018 Oct 15. doi: 10.1002/jcb.27701. and titled:

Protein translation associated to PERK arm is a new target for regulation of metainflammation: A connection with hepatocyte cholesterol.

Authors of this article are:

Galindo-Hernández O, Córdova-Guerrero I, Díaz-Rubio LJ, Pulido-Capiz Á, Díaz-Villanueva JF, Castañeda-Sánchez CY, Serafín-Higuera N, García-González V.

A summary of the article is shown below:

Endoplasmic reticulum stress is a cellular phenomenon that has been associated with metabolic disorders, contributing to the development of obesity, fatty liver disease, and dyslipidemias. Under metabolic overload conditions, in cells with a high protein-secretory activity, such as hepatocytes and Langerhans β cells, the unfolded protein response (UPR) is critical in to maintain protein homeostasis (proteostasis). UPR integrated by a tripartite signaling system, through activating transcription factor 6, protein kinase R-like endoplasmic reticulum kinase (PERK), and inositol-requiring enzyme 1, regulates gene transcription and translation to resolve stress and conserve proteostasis. In the current study, we demonstrated in hepatocytes under metabolic overload by saturated palmitic and stearic fatty acids, through activation of PERK signaling and CCAAT-enhancer-binding protein homologous protein (CHOP) transcription factor, an association with the expression of cyclooxygenase 2. More important, isolated exosomes from supernatants of macrophages exposed to lipopolysaccharides can also induce a metainflammation phenomenon, and when treated on hepatocytes, induced a rearrangement in cholesterol metabolism through sterol regulatory element-binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLR), apolipoprotein A-I, and ABCA1. Moreover, we demonstrate the cellular effect of terpene-derived molecules, such as cryptotanshinone, isolated of plant Salvia brandegeei, regulating metainflammatory conditions through PERK pathway in both hepatocytes and β cells. Our data suggest the presence of a modulatory mechanism on specific protein translation process. This effect could be mediated by eukaryotic initiation factor-4A, evaluating salubrinal as a control molecule. Likewise, the protective mechanisms of unsaturated fatty acids, such as oleic and palmitoleic acid were confirmed. Therefore, modulation of metainflammation suggests a new target through PERK signaling in cells with a high secretory activity, and possibly the regulation of cholesterol in hepatocytes is promoted via exosomes.

Check out the article’s website on Pubmed for more information:



This article is a good source of information and a good way to become familiar with topics such as:

PERK pathway;exosomes;hepatocytes;metainflammation;proteostasis;terpenes

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