pone.0269564.g007.tif (1.81 MB)

TUDCA decreases ER stress in HOX neonatal rat lungs.

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posted on 2022-08-26, 17:46 authored by Kirkwood A. Pritchard Jr., Xigang Jing, Michelle Teng, Clive Wells, Shuang Jia, Adeleye J. Afolayan, Jason Jarzembowski, Billy W. Day, Stephen Naylor, Martin J. Hessner, G. Ganesh Konduri, Ru-Jeng Teng

(A) The expression levels of ER stress markers (P-PERK 0.6±0.1-fold, p<0.001, n = 5; PERK 0.7±0.1-fold, p = 0.00364, n = 5; P-IRE1α 0.6±0.0-fold, p<0.001, n = 5; IRE1α 0.6±0.1-fold, p<0.001, n = 5; GRP78 0.8±0.1-fold, p<0.001, n = 5; cleaved ATF6 0.1±0.0-fold, p<0.001, n = 5; spliced XBP1 0.3±0.0-fold, p<0.001, n = 5; 2 males and 3 females) are all decreased while the N-glycosylated VEGFR2 is increased (3.5±0.2-fold, p<0.001, n = 5) in HOX neonatal lungs at P10 indicating TUDCA can attenuate hyperoxia-induced ER stress. (B) TUDCA also decreases ER stress-mediated apoptosis as evidenced by the decreased CHOP (0.6±0.1-fold, p = 0.002001, n = 5), caspase-12 (0.7±0.1-fold, p<0.001, n = 5), cleaved caspase-12 (0.6±0.1-fold, p<0.001, n = 5), and BAX/BCl2 ratio (0.2±0.0-fold, p<0.001, n = 5). (C) In IHC stain, P-IRE1α levels are decreased (40.8±3.5 A.U. vs 53.1±5.0 A.U., p<0.001, n = 6, 3 for each sex) in chronic hyperoxia exposed neonatal rat lungs by TUDCA. (D) The dilated ER structure, ER-mitochondria separation, and mitochondrial fission are seen both in AT2 (20,000x magnification) and EC (30,000x magnification) while TUDCA partially reverses the structural changes under the electron microscope. LB: lamellar body in AT2. M: mitochondria. Scale bar = 100 μm for light microscope and = 500 nm for electron microscope. *: p<0.05.