Unfolding protein response signaling is involved in development, maintenance, and regression of the corpus luteum during the bovine estrous cycle

Park, Hyo-Jin; Park, Sun-Ji; Koo, Deog‐Bon; Kong, Il‐Keun; Kim, Min Kyu; Kim, Jin Man; Choi, Myung‐Sook; Park, Young-Ho; Kim, Sun-Uk; Chang, Kyu‐Tae; Park, Choon‐Keun; Chae, Jung‐Il; Lee, Dong Seok

doi:10.1016/j.bbrc.2013.10.056

Cited by 30 publications

(34 citation statements)

References 26 publications

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“…Indeed, our results further suggested by previous data and which study revealed that the ERS-mediated apoptotic pathway might be involved in the bovine CL regression during estrous cycle. 16 Indeed, CHOP was detected in bovine and rat's CL regression; in addition, the phospho-JNK signaling pathway was also detected in the bovine CL regression, combined with our result that caspase 12 is involved in rat's CL regression. All results suggested that the ERS-mediated apoptosis pathway might be involved in the CL regression through CHOP, pJNK, and caspase-12 signaling pathways.…”

Section: Discussionsupporting

confidence: 73%

Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway Is Involved in Corpus Luteum Regression in Rats

et al. 2015

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Endoplasmic reticulum stress (ERS), which is a novel pathway of regulating cellular apoptosis and the function of ERS during corpus luteum (CL) regression, is explored. Early-luteal stage (day 2), mid-luteal stage (day 7), and late-luteal stage (day 14 and 20) were induced, and the apoptosis of luteal cells was detected by a terminal 2 0 -deoxyuridine 5 0 -triphosphate nick-end labeling (TUNEL) assay. The apoptotic cells were increased with the regression of CL, especially during the late-luteal stage. The ERS markers glucose-regulated protein 78 (Grp78), CCAAT/enhancer-binding protein homologous protein (CHOP), X-box binding protein 1 (XBP1), activating transcription factor 6a (ATF6a), eukaryotic initiation factor 2a (eIF2a), inositol-requiring protein 1a (IRE1a), caspase 12, and apoptosis marker caspase 3 were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemistry, in agreement with the results of the TUNEL assay; the expression levels of CHOP, caspase 12, and caspase 3 were increased during the process of CL regression. Luteal cells were isolated and cultured in vitro, and the apoptosis of luteal cells was induced by prostaglandin F2a. The ERS was attenuated by the ERS inhibitor tauroursodeoxycholic acid, and the apoptotic rate was analyzed by flow cytometry. The ERS markers Grp78, CHOP, XBP1s, ATF6a, eIF2a, IRE1a, caspase 12, and apoptotic execute marker caspase 3 were analyzed by real-time PCR and immunofluorescence, and the results suggested that the expression of CHOP, caspase 12, and caspase 3 were increased, and there was increased apoptosis of luteal cells. But the expression of IRE1a/XBP1s and eIF2a was not detected. Taken together, the ERS is involved in the CL regression of rats through the CHOP and caspase 12 pathway.

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Section: Discussionsupporting

confidence: 73%

Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway Is Involved in Corpus Luteum Regression in Rats

et al. 2015

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“…Interestingly, pIRE1α and CHOP have been found to be regulated in both the adaptive response and ERS-mediated apoptosis. During the CL regression stage, increased expression of pJNK and CHOP, two components of ERS-mediated apoptotic cascades, occurs before the increased levels of cleaved caspase-3 are observed (Park et al 2013). These results are further supported by Park's data showing that the ERS and UPR are involved in the mouse CL lifespan, and that the secretion of P 4 is affected by the UPR (Park et al 2014).…”

Section: Involvement Of Ers Response In Corpus Luteum Development Andsupporting

confidence: 56%

“…The expression of Grp78/Bip (immunoglobulin heavy chain binding protein in pre-B cells) is increased during the maintenance stage and rapidly decreases at the regression stage. Additionally, UPR genes are found to be involved in luteal phase progression during the estrous cycle, and this finding suggests that Grp78/Bip, ATF6α, and XBP1 act as ER chaperones to initiate CL development and maintenance of the CL (Park et al 2013). Grp78 might be involved in CL formation by regulating the expression of luteinizing hormone receptor (Kogure et al 2013).…”

Section: Involvement Of Ers Response In Corpus Luteum Development Andmentioning

confidence: 98%

The roles of endoplasmic reticulum stress response in female mammalian reproduction

et al. 2015

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Endoplasmic reticulum stress (ERS) activates a protective pathway, called the unfold protein response, for maintaining cellular homeostasis, but cellular apoptosis is triggered by excessive or persistent ERS. Several recent studies imply that the ERS response might have broader physiological roles in the various reproductive processes of female mammals, including embryo implantation, decidualization, preimplantation embryonic development, follicle atresia, and the development of the placenta. This review summarizes the existing data concerning the molecular and biological roles of the ERS response. The study of the functions of the ERS response in mammalian reproduction might provide novel insights into and an understanding of reproductive cell survival and apoptosis under physiological and pathological conditions. The ERS response is a novel signaling pathway for reproductive cell survival and apoptosis. Infertility might be a result of disturbing the ERS response during the process of female reproduction.

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“…All three UPR signaling pathways, including adaptive or apoptotic signaling molecules (Grp78, p-eIF2α, ATF4, CHOP, ATF6, p-IRE1α, XBP1 s and p-JNK), are activated during luteal-phase progression during the estrous cycle of bovines] (Park et al, 2013a) and mice (Park et al, 2014). Pro-apoptotic signaling molecules such as cleaved caspase3, JNK, and CHOP were detected, and JNK activation and CHOP expression via ER stress–mediated pro-apoptotic signaling cascades occurred prior to caspase3 activation during the regression stage of the corpus luteum (Urano et al, 2000; McCullough et al, 2001; Novoa et al, 2001; Marciniak et al, 2004; Yamaguchi and Wang 2004; Woo et al, 2009; Park et al, 2013a; Park et al, 2014). Furthermore, the dynamic change of these molecules seems to have some connection with the steroidogenic enzymes, which suggests that the UPR may influence the expression of steroidogenic enzymes (Park et al, 2013a; Park et al, 2013b).…”

Section: Activation Of the Upr In The Ovarian Cyclementioning

confidence: 99%

“…The corpus luteum develops from the follicle cells surrounding the ovulatory follicle and functions as a major site for the synthesis and secretion of progesterone. Some studies have indicated a link between the UPR and progesterone synthesis (Park et al, 2013a). In addition to their functions in ovarian physiology, ER stress and the UPR may also play a role in ovarian pathology.…”

Section: Introductionmentioning

confidence: 99%

Dual role for the unfolded protein response in the ovary: adaption and apoptosis

Qiao

2016

Protein &Amp; Cell

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The endoplasmic reticulum (ER) is the principal organelle responsible for several specific cellular functions including synthesis and folding of secretory or membrane proteins, lipid metabolism, and Ca2+ storage. Different physiological as well as pathological stress conditions can, however, perturb ER homeostasis, giving rise to an accumulation of unfolded or misfolded proteins in the ER lumen, a condition termed ER stress. To deal with an increased folding demand, cells activate the unfolded protein response (UPR), which is initially protective but can become detrimental if ER stress is severe and prolonged. Accumulating evidence demonstrates a link between the UPR and ovarian development and function, including follicular growth and maturation, follicular atresia, and corpus luteum biogenesis. Additionally, ER stress and the UPR may also play an important role in the ovary under pathological conditions. Understanding the molecular mechanisms related to the dual role of unfolded protein response in the ovarian physiology and pathology may reveal the pathogenesis of some reproductive endocrine diseases and provide a new guidance to improve the assisted reproductive technology. Here we review the current literature and discuss concepts and progress in understanding the UPR, and we also analyze the role of ER stress and the UPR in the ovary.

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Unfolding protein response signaling is involved in development, maintenance, and regression of the corpus luteum during the bovine estrous cycle

Cited by 30 publications

References 26 publications

Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway Is Involved in Corpus Luteum Regression in Rats

Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway Is Involved in Corpus Luteum Regression in Rats

The roles of endoplasmic reticulum stress response in female mammalian reproduction

Dual role for the unfolded protein response in the ovary: adaption and apoptosis

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