PMID- 28624282 OWN - NLM STAT- MEDLINE DCOM- 20180420 LR - 20181202 IS - 1525-3198 (Electronic) IS - 0022-0302 (Linking) VI - 100 IP - 8 DP - 2017 Aug TI - Effect of endoplasmic reticulum stress on metabolic and stress signaling and kidney-specific functions in Madin-Darby bovine kidney cells. PG - 6689-6706 LID - S0022-0302(17)30591-X [pii] LID - 10.3168/jds.2016-12406 [doi] AB - Recent studies demonstrated induction of endoplasmic reticulum (ER) stress in tissues of cows after parturition, but knowledge about the effect of ER stress on important cellular processes, such as critical signaling and metabolic pathways, in cattle is scarce. Thus, the present study aimed to investigate the effect of ER stress induction on nuclear factor-kappaB (NF-kappaB), nuclear factor E2-related factor 2 (Nrf2), and sterol regulatory element-binding protein (SREBF1) pathway in Madin-Darby bovine kidney (MDBK) cells, a widely used in vitro model in ruminant research. To consider the kidney origin of MDBK cells, the effect on renal distal tubular cell-specific functions, such as transport processes and regulation of 1,25(OH)(2)D(3) levels, was also studied. Treatment of MDBK cells with 2 different ER stress inducers, thapsigargin (TG) and tunicamycin (TM), strongly induced ER stress as evident from induction of ER stress target genes, increased phosphorylation of PKR-like ER kinase, and enhanced splicing of X-box binding protein 1. The TM decreased the protein concentration of NF-kappaB p50 and the mRNA levels of the NF-kappaB target genes. Likewise, TG decreased the mRNA concentration of tumor necrosis factor and tended to decrease NF-kappaB p50 protein and mRNA levels of NF-kappaB target genes. The mRNA levels of most of the Nrf2 target genes investigated were reduced by TG and TM in MDBK cells. Both ER stress inducers reduced the mRNA levels of SREBF1 and its target genes in MDBK cells. Interestingly, TG decreased, but TM increased the mRNA level of the Ca(2+) binding protein calbindin 1, whereas the mRNA level of the plasma membrane Ca(2+)-transporting ATPase 1 remained unchained. The mRNA level of the cytochrome P450 component 24A1 involved in 1alpha-hydroxylation of 25(OH)D(3) was strongly elevated, whereas the mRNA level of the cytochrome P450 component 27A1 catalyzing the breakdown of 1,25(OH)(2)D(3) was markedly reduced by both ER stress inducers. The concentration of 1,25(OH)(2)D(3) in the supernatant of MDBK cells was increased by approximately 15% by both TG and TM. The present study indicates that under conditions of ER stress, critical signaling pathways, such as NF-kappaB, Nrf2, and SREBF1, are inhibited, whereas the formation of 1,25(OH)(2)D(3) is stimulated in bovine MDBK cells. Future studies are necessary to clarify the physiological relevance of these findings. CI - Copyright (c) 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved. FAU - Chiappisi, E AU - Chiappisi E AD - Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany. FAU - Ringseis, R AU - Ringseis R AD - Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany. FAU - Eder, K AU - Eder K AD - Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany. FAU - Gessner, D K AU - Gessner DK AD - Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany. Electronic address: denise.gessner@ernaehrung.uni-giessen.de. LA - eng PT - Journal Article DEP - 20170616 PL - United States TA - J Dairy Sci JT - Journal of dairy science JID - 2985126R RN - 0 (NF-kappa B) RN - 0 (X-Box Binding Protein 1) RN - 11089-65-9 (Tunicamycin) RN - 67526-95-8 (Thapsigargin) SB - IM MH - Animals MH - Cattle MH - Cell Line MH - *Endoplasmic Reticulum Stress MH - Female MH - Kidney Tubules, Distal MH - NF-kappa B MH - *Signal Transduction MH - Thapsigargin/pharmacology MH - Tunicamycin/pharmacology MH - X-Box Binding Protein 1/*metabolism OTO - NOTNLM OT - Madin-Darby bovine kidney cell OT - endoplasmic reticulum stress OT - inflammation OT - vitamin D EDAT- 2017/06/19 06:00 MHDA- 2018/04/21 06:00 CRDT- 2017/06/19 06:00 PHST- 2016/12/06 00:00 [received] PHST- 2017/04/28 00:00 [accepted] PHST- 2017/06/19 06:00 [pubmed] PHST- 2018/04/21 06:00 [medline] PHST- 2017/06/19 06:00 [entrez] AID - S0022-0302(17)30591-X [pii] AID - 10.3168/jds.2016-12406 [doi] PST - ppublish SO - J Dairy Sci. 2017 Aug;100(8):6689-6706. doi: 10.3168/jds.2016-12406. Epub 2017 Jun 16.