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- W1444704654 abstract "This study investigates calcium dysregulation during the initial phase of the brefeldin A (BFA)-induced sarco/endoplasmic reticulum (SR/ER) stress response in vascular smooth muscle cells (VSMCs). BFA is most commonly cited as initiating this response through an accumulation of unfolded protein in the lumen due to blockage of protein transport from the ER to the Golgi apparatus. However, BFA's effect on calcium signals within the SR is poorly understood. Based on our observations, acute exposure to BFA causes a non-significant initial wave of SR calcium movement, which is minor compared to that induced by other popular ER stressors such as thapsigargin and tunicamycin. Time-course studies were conducted to observe the effects of BFA exposure on SR calcium over six time points (0, 1, 3, 6, 9, 12 hrs). We observed that BFA caused an approximate 50% decrease in SR calcium concentration within the first hour of exposure. Interestingly, the unfolded protein response (UPR) was detected after 6 hours of treatment, and was associated with slight recovery of SR calcium concentration. We have therefore concluded that the SR calcium drop characteristic of the cellular stress response occurs prior to the initiation of the UPR, rather than, as suggested before, being a result of its many corrective pathways. We reason that this calcium drop is potentially the trigger setting off the entire SR/ER stress process. This study was supported by a grant from the Canadian Institutes of Health Research [MOP-111266] to C.V.B. & M.E." @default.
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- W1444704654 date "2015-04-01" @default.
- W1444704654 modified "2023-10-16" @default.
- W1444704654 title "Early Transient Sarcoplasmic Reticulum Calcium Decrease Prior to Initiation of Unfolded Protein Response in Vascular Smooth Muscle Cells" @default.
- W1444704654 doi "https://doi.org/10.1096/fasebj.29.1_supplement.782.6" @default.
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