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ER a5

Marie-Laure Calvez, Nathalie Benz, Florentin Huguet, Aude Saint-Pierre, Elise Rouillé, Christelle Coraux, Claude Férec, Mathieu Kerbiriou, Pascal Trouvé
Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) chloride (Cl-) channel regulated by protein kinases, phosphatases, divalent cations and by protein-protein interactions. Among protein-protein interactions, we previously showed that Annexin A5 (AnxA5) binds to CFTR and is involved in the channel localization within membranes and in its Cl- channel function. The deletion of phenylalanine at position 508 (F508del) is the most common mutation in CF which leads to an altered protein (F508del-CFTR) folding with a nascent protein retained within the ER and is quickly degraded...
2017: PloS One
Marit Wiersma, Roelien A M Meijering, Xiao-Yan Qi, Deli Zhang, Tao Liu, Femke Hoogstra-Berends, Ody C M Sibon, Robert H Henning, Stanley Nattel, Bianca J J M Brundel
BACKGROUND: Derailment of proteostasis, the homeostasis of production, function, and breakdown of proteins, contributes importantly to the self-perpetuating nature of atrial fibrillation (AF), the most common heart rhythm disorder in humans. Autophagy plays an important role in proteostasis by degrading aberrant proteins and organelles. Herein, we investigated the role of autophagy and its activation pathway in experimental and clinical AF. METHODS AND RESULTS: Tachypacing of HL-1 atrial cardiomyocytes causes a gradual and significant activation of autophagy, as evidenced by enhanced LC3B-II expression, autophagic flux and autophagosome formation, and degradation of p62, resulting in reduction of Ca(2+) amplitude...
October 24, 2017: Journal of the American Heart Association
Eunhee Kim, Kazuko Sakata, Francesca-Fang Liao
The unfolded protein response (UPR) in the endoplasmic reticulum (ER) and the cytoplasmic heat stress response are two major stress response systems necessary for maintaining proteostasis for cellular health. Failure of either of these systems, such as in sustained UPR activation or in insufficient heat shock response activation, can lead to the development of neurodegeneration. Alleviation of ER stress and enhancement of heat shock response through heat shock factor 1 (HSF1) activation have previously been considered as attractive potential therapeutic targets for Alzheimer's disease (AD)-a prevalent and devastating tauopathy...
July 2017: PLoS Genetics
J Osacka, L Horvathova, Z Majercikova, Alexander Kiss
OBJECTIVE: Fos protein expression in catecholamine-synthesizing neurons of the substantia nigra (SN) pars compacta (SNC, A8), pars reticulata (SNR, A9), and pars lateralis (SNL), the ventral tegmental area (VTA, A10), the locus coeruleus (LC, A6) and subcoeruleus (sLC), the ventrolateral pons (PON-A5), the nucleus of the solitary tract (NTS-A2), the area postrema (AP), and the ventrolateral medulla (VLM-A1) was quantitatively evaluated aft er a single administration of asenapine (ASE) (designated for schizophrenia treatment) in male Wistar rats preconditioned with a chronic unpredictable variable mild stress (CMS) for 21 days...
April 25, 2017: Endocrine Regulations
Marcos A Carpio, Michael Michaud, Wenping Zhou, Jill K Fisher, Loren D Walensky, Samuel G Katz
B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) is a BCL-2 family protein with high homology to the multidomain proapoptotic proteins BAX and BAK, yet Bok(-/-) and even Bax(-/-)Bok(-/-) and Bak(-/-)Bok(-/-) mice were reported to have no overt phenotype or apoptotic defects in response to a host of classical stress stimuli. These surprising findings were interpreted to reflect functional compensation among the BAX, BAK, and BOK proteins. However, BOK cannot compensate for the severe apoptotic defects of Bax(-/-)Bak(-/-) mice despite its widespread expression...
June 9, 2015: Proceedings of the National Academy of Sciences of the United States of America
Hongmin Luo, Jinko Sawashita, Geng Tian, Yingye Liu, Lin Li, Xin Ding, Zhe Xu, Mu Yang, Hiroki Miyahara, Masayuki Mori, Jinze Qian, Yaoyong Wang, Keiichi Higuchi
Mouse senile amyloidosis is a disorder in which apolipoprotein A-II deposits extracellularly in many organs as amyloid fibrils (AApoAII). In this study, we intravenously injected 1 μg of isolated AApoAII fibrils into R1.P1-Apoa2(c) mice, to induce AApoAII amyloidosis. We observed that the unfolded protein response was induced by deposition of AApoAII amyloid. We found that the mRNA and the protein expression levels of heat shock protein A5 (HSPA5; also known as glucose-regulated protein 78) were increased in the liver with AApoAII amyloid deposits...
March 2015: Laboratory Investigation; a Journal of Technical Methods and Pathology
Arisa Higa, Said Taouji, Stéphanie Lhomond, Devon Jensen, Martin E Fernandez-Zapico, Jeremy C Simpson, Jean-Max Pasquet, Randy Schekman, Eric Chevet
ATF6α, a membrane-anchored transcription factor from the endoplasmic reticulum (ER) that modulates the cellular response to stress as an effector of the unfolded-protein response (UPR), is a key player in the development of tumors of different origin. ATF6α activation has been linked to oncogenic transformation and tumor maintenance; however, the mechanism(s) underlying this phenomenon remains elusive. Here, using a phenotypic small interfering RNA (siRNA) screening, we identified a novel role for ATF6α in chemoresistance and defined the protein disulfide isomerase A5 (PDIA5) as necessary for ATF6α activation upon ER stress...
May 2014: Molecular and Cellular Biology
Nathalie Benz, Sophie Le Hir, Caroline Norez, Mathieu Kerbiriou, Marie-Laure Calvez, Frédéric Becq, Pascal Trouvé, Claude Férec
Cystic fibrosis (CF), the most common autosomal recessive disease in Caucasians, is due to mutations in the CFTR gene. F508del, the most frequent mutation in patients, impairs CFTR protein folding and biosynthesis. The F508del-CFTR protein is retained in the endoplasmic reticulum (ER) and its traffic to the plasma membrane is altered. Nevertheless, if it reaches the cell surface, it exhibits a Cl(-) channel function despite a short half-life. Pharmacological treatments may target the F508del-CFTR defect directly by binding to the mutant protein or indirectly by altering cellular proteostasis, and promote its plasma membrane targeting and stability...
2014: PloS One
Natasha N Mott, Elena Pinceti, Yathindar S Rao, Magdalena M Przybycien-Szymanska, Sarah A Prins, Cody L Shults, Xinli Yang, Marc J Glucksman, James L Roberts, Toni R Pak
Recent clinical evidence suggests that the neuroprotective and beneficial effects of hormone therapy may be limited by factors related to age and reproductive status. The patient's age and length of time without circulating ovarian hormones are likely to be key factors in the specific neurological outcomes of hormone therapy. However, the mechanisms underlying age-related changes in hormone efficacy have not been determined. We hypothesized that there are intrinsic changes in estrogen receptor β (ERβ) function that determine its ability to mediate the actions of 17β-estradiol (E2) in brain regions such as the ventral hippocampus...
March 2014: Molecular & Cellular Proteomics: MCP
Myrtani Pieri, Charalambos Stefanou, Apostolos Zaravinos, Kamil Erguler, Kostas Stylianou, George Lapathitis, Christos Karaiskos, Isavella Savva, Revekka Paraskeva, Harsh Dweep, Carsten Sticht, Natassa Anastasiadou, Ioanna Zouvani, Demetris Goumenos, Kyriakos Felekkis, Moin Saleem, Konstantinos Voskarides, Norbert Gretz, Constantinos Deltas
Thin-basement-membrane nephropathy (TBMN) and Alport syndrome (AS) are progressive collagen IV nephropathies caused by mutations in COL4A3/A4/A5 genes. These nephropathies invariably present with microscopic hematuria and frequently progress to proteinuria and CKD or ESRD during long-term follow-up. Nonetheless, the exact molecular mechanisms by which these mutations exert their deleterious effects on the glomerulus remain elusive. We hypothesized that defective trafficking of the COL4A3 chain causes a strong intracellular effect on the cell responsible for COL4A3 expression, the podocyte...
February 2014: Journal of the American Society of Nephrology: JASN
Aili Cao, Qi Li, Peihao Yin, Yang Dong, Hailian Shi, Li Wang, Guang Ji, Jianqun Xie, Dazheng Wu
In the present study, we investigate the effect of curcumin, a major active component isolated from rhizomes of Curcuma longa, on the cytotoxicity of three human carcinoma cell lines (AGS, HT-29 and MGC803) in gastrointestinal tract and a normal gastric epithelial cell line GES-1, and the mechanism of curcumin-induced apoptosis. The results indicated that curcumin inhibited the gastrointestinal carcinoma cell growth in a dose-dependent manner and cytotoxicity was more towards the gastric carcinoma cell AGS and colon carcinoma cell HT-29 compared to normal gastric cell GES-1, and increased externalization of phosphatidylserine residue was observed by Annexin V/PI staining in the two cell lines...
November 2013: Apoptosis: An International Journal on Programmed Cell Death
K Brasseur, V Leblanc, F Fabi, S Parent, C Descôteaux, G Bérubé, E Asselin
As we previously showed, we have synthesized a new family of 17β-estradiol-platinum(II) hybrids. Earlier studies revealed the VP-128 hybrid to show high efficiency compared with cisplatin toward hormone-dependent breast cancer cells. In the present research, we have studied the antitumor activity of VP-128 in vitro and in vivo against ovarian cancer. In nude mice with ovarian xenografts, VP-128 displayed selective activity toward hormone-dependent tumors and showed higher efficiency than cisplatin to inhibit tumor growth...
July 2013: Endocrinology
Arvind M Korwar, Hemangi S Bhonsle, Vikram S Ghole, Kachru R Gawai, Chaitanyananda B Koppikar, Mahesh J Kulkarni
Breast cancer, especially ER positive/HER2/neu negative IDC, is the predominant subtype of invasive ductal carcinoma. Although proteomic approaches have been used towards biomarker discovery in clinical breast cancer, ER positive/HER2/neu negative IDC is the least studied subtype. To discover biomarkers, as well as to understand the molecular events associated with disease progression of estrogen receptor positive/HER2/neu negative subtype of invasive ductal carcinoma, differential protein expression profiling was performed by using LC-MS(E) (MS at elevated energy)...
January 2013: Omics: a Journal of Integrative Biology
Babak Baban, Jun Yao Liu, Mahmood S Mozaffari
We tested the hypotheses that a) type 2 diabetes increases endoplasmic reticulum (ER) stress response, production of pro-inflammatory cytokines and kidney cell death and b) downregulations of renal indoleamine 2,3-dioxygenase (IDO) and programmed death-1 (PD-1) contribute to exacerbated inflammation and tissue injury. The growth arrest and DNA damage-inducible protein 153 (GADD153; a marker of ER stress response), inflammatory cytokines and cell death were determined in the context of assessment of IDO and PD-1 in an animal model of type 2 diabetic nephropathy (i...
April 2013: Experimental and Molecular Pathology
Mirriam E Nyenje, Nicoline F Tanih, Ezekiel Green, Roland N Ndip
This study assessed the antimicrobial susceptibility of 51 Listeria ivanovii and 33 Enterobacter cloacae strains isolated from various ready-to-eat foods sold in Alice, South Africa. Isolates were identified using standard microbiological tests and further confirmed using API 20E and API Listeria kits. The disc diffusion technique was used to screen for antimicrobial susceptibility against 15 antimicrobials; minimum inhibitory concentration of five antibiotics was determined by the broth dilution method. All the strains of E...
September 2012: International Journal of Environmental Research and Public Health
Chunyang Jiang, Shun Zhang, Hongliang Liu, Qiang Zeng, Tao Xia, Yihu Chen, Gang Kuang, Guodong Zhao, Xue Wu, Xiaofei Zhang, Aiguo Wang
Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants. As one of the dominant congeners, 2,2', 4,4'-tetrabromodiphenyl ether (PBDE-47) has been shown to be neurotoxic to neuronal cells although the mechanisms remain unclear. To test whether PBDE-47's toxicity was related to endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), human neuroblastoma cells (SH-SY5Y cells) were treated with different concentrations of PBDE-47. Reactive oxygen species (ROS), apoptosis and the expressions of the inositol-requiring enzyme 1 (IRE1) pathway-related molecules were detected...
June 20, 2012: Toxicology Letters
Wei Ding, Lei Yang, Minmin Zhang, Yong Gu
Apoptosis contributes to tubular epithelial cell death and atrophy in aldosterone (Aldo)-induced renal injury. This study aimed to determine mechanisms underlying Aldo-induced reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress in tubular epithelial cells. Intracellular ROS generation was evaluated by 2',7'-dichlorofluorescin diacetate fluorescence. Apoptosis was detected by annexin V/propidium iodide staining and flow cytometry. ER stress induced protein and mRNA were evaluated by Western blot and real-time PCR, respectively...
February 17, 2012: Biochemical and Biophysical Research Communications
V Pernet, S Joly, D Dalkara, O Schwarz, F Christ, D Schaffer, J G Flannery, M E Schwab
Nogo-A, an axonal growth inhibitory protein known to be mostly present in CNS myelin, was upregulated in retinal ganglion cells (RGCs) after optic nerve injury in adult mice. Nogo-A increased concomitantly with the endoplasmic reticulum stress (ER stress) marker C/EBP homologous protein (CHOP), but CHOP immunostaining and the apoptosis marker annexin V did not co-localize with Nogo-A in individual RGC cell bodies, suggesting that injury-induced Nogo-A upregulation is not involved in axotomy-induced cell death...
July 2012: Cell Death and Differentiation
Pablo N De Francesco, Juan M Mucci, Romina Ceci, Carlos A Fossati, Paula A Rozenfeld
Fabry disease is an X-linked lysosomal storage disorder (LSD) due to deficiency of the enzyme α-galactosidase A, resulting in intracellular deposition of globotriaosylceramide (Gb3). Accumulation of Gb3 is probably related to tissue and organ dysfunctions. Diverse pathological mechanisms are elicited in LSDs, giving together the phenotypic expression of each disease. The purpose of the present study is to investigate if apoptosis could play a role in Fabry disease pathogenesis and to understand the mechanisms involved in the proapoptotic state...
November 2011: Molecular Genetics and Metabolism
Nina Weichert, Eva Kaltenborn, Andreas Hector, Markus Woischnik, Andrea Schams, Andreas Holzinger, Sunčana Kern, Matthias Griese
BACKGROUND: ABCA3 transporter (ATP-binding cassette transporter of the A subfamily) is localized to the limiting membrane of lamellar bodies, organelles for assembly and storage of pulmonary surfactant in alveolar epithelial type II cells (AECII). It transports surfactant phospholipids into lamellar bodies and absence of ABCA3 function disrupts lamellar body biogenesis. Mutations of the ABCA3 gene lead to fatal neonatal surfactant deficiency and chronic interstitial lung disease (ILD) of children...
January 7, 2011: Respiratory Research
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