Abstract
Objective: The circadian rhythm is one of the primary regulatory systems with near 24-hour oscillations. It has a crucial role in regulating physiological conditions in the human body, including body temperature and the secretion of hormones. Numerous disorders, such as cancer and diabetes, have been linked to disruptions of the cellular circadian rhythm. Herein, we aimed to investigate the relationship between the circadian rhythm and unfolded protein response (UPR) signaling, which is one of the important physiological mechanisms in mammalian cells and has recently been associated with drug resistance, invasion and metastasis in cancer. Material and Method: Human embryonic kidney cell line HEK293 was provided from the American Type Culture Collection and propagated in DMEM containing 10% FBS and growth ingredients. For in vitro circadian synchronization, cells were exposed to 50% and then the oscillation pattern of gene and protein expression of UPR-related target genes was analyzed by agarose gel electrophoresis and immunoblotting, respectively. The oscillation pattern was commented on through curve-fitting analysis. Result and Discussion: Our findings demonstrated that UPR components, including IRE1α, XBP-1s, eIF2α, phospho(Ser51)-eIF2α, PERK, ATF4, GADD34 and ATF6, tightly exhibit oscillation patterns under a circadian rhythm on a 48-hour time scale like the PER1 gene that is a core component of the circadian rhythm. Moreover, endoplasmic reticulum (ER) stress genes, BiP/GRP78 and CHOP, were similar to UPR components under the circadian rhythm. Additionally, we found the activation of UPR signaling harmoniously modulated with the circadian rhythm. Present data indicated that the expression level of UPR components exhibited strict oscillation under the circadian rhythm. Our findings may guide experimental studies of new-generation UPR-targeted drugs to be developed to treat various pathologies in accordance with the circadian rhythm.
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
