ER Stress Proteins in Autoimmune and Inflammatory Diseases

Morito, Daisuke; Nagata, Kazuhiro

doi:10.3389/fimmu.2012.00048

Cited by 62 publications

(60 citation statements)

References 130 publications

(167 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, more and more evidences indicate that GRP78 plays diverse roles beyond the ER (Quinones et al 2008;Morito & Nagata 2012). Studies have shown that GRP78 is expressed on the cell surface in many tissue types, and involved in transducing signals from ligands as disparate as activated α2-macroglobulin and antibodies (Gonzalez-Gronow et al 2009;Zhang et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Molecular cloning and expression analysis of glucose-regulated protein 78 (GRP78) gene in silkworm Bombyx mori

Xing-zi

2013

Biologia

View full text Add to dashboard Cite

GRP78 (78 kDa glucose-regulated protein), also known as BiP (immunoglobulin heavy-chain-binding protein), is an essential regulator of endoplasmic reticulum (ER) homeostasis because of its multiple functions in protein folding, ER calcium binding, and controlling of the activation of transmembrane ER stress sensors. In this report, we cloned the full-length cDNA of GRP78 from silkworm Bombyx mori (BmGRP78). It is 2645 bp, including an open reading frame (ORF) of 1977 bp encoding a polypeptide of 658 amino acids. We sequenced the ORF sequence from genomic DNA, and found only one intron (104 bp) existed in Bmgrp78 gene structure. The deduced amino acid sequence of Bmgrp78 carries the ER retention signal KDEL at its C-terminus and is highly homologous to GRP78 of Fenneropenaeus chinensis (83.59%) and Homo sapiens (80.27%). RT-PCR analysis shows that Bmgrp78 is ubiquitously expressed in tissues of silkworm. Heat shock over 35• C notably enhanced the expression of Bmgrp78 in head tissues. In response to starvation, the transcript level of Bmgrp78 in head tissues was 2.8-fold (at WS stage) and 3.2-fold (at SD1 stage) higher than the control level, but it remained stable in the midgut tissues. After silkworms were challenged by bacteria, the relative expression level of Bmgrp78 in midgut was up-regulated and reached maximal level at 24 hour after injection, and remained higher level than that of controls at about 48 hour post challenge. We infer that BmGRP78 may play important roles in chaperoning, protein folding and immune function of silkworm.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular cloning and expression analysis of glucose-regulated protein 78 (GRP78) gene in silkworm Bombyx mori

Xing-zi

2013

Biologia

View full text Add to dashboard Cite

show abstract

“…Interestingly, chronic ER stress has been implicated in the pathology of a number of conditions like diabetes, traumatic brain injury, sepsis and neurodegenerative diseases (8-10). Therefore, studying the ER stress response in both an in vitro and in vivo context can help uncover and shed light on the pathology and development of these diseases.…”

Section: Introductionmentioning

confidence: 99%

Modeling Acute ER Stress in Vivo and in Vitro

Abdullahi

Stanojcic

Parousis

et al. 2017

Shock

View full text Add to dashboard Cite

The Endoplasmic Reticulum (ER) is a critical organelle that synthesizes secretory proteins and serves as the main calcium storage site of the cell. The accumulation of unfolded proteins at the ER results in ER stress. Although the association between ER stress and the pathogenesis of many metabolic conditions have been well characterized using both in vivo and in vitro models, no standardized model concerning ER stress exists. Here we report a standardized model of ER stress using two well characterized ER stress inducing agents, thapsigargin and tunicamycin. Our aim in this current study was two-fold: (1) to characterize and establish which agent is optimal for in vitro use to model acute ER stress and (2) to evaluate which agent is optimal for in vivo use. To study aim 1 we used two well-established metabolic cell lines; human hepatocellular carcinoma (HepG2s) and differentiated mouse adipocytes (3T3-L1). In aim 2 we utilized C57BL/6J mice that were randomized into 3 treatment groups of sham, thapsigargin, and tunicamycin. Our in vitro results showed that tunicamycin worked as a rapid and efficacious inducer of ER stress in adipocytes consistently, whereas thapsigargin and tunicamycin were equally effective in inducing ER stress in hepatocytes. In regards to our in vivo results, we saw that tunicamycin was superior in not only inducing ER stress but also recapturing the metabolic alterations associated with ER stress. Thus, our findings will help guide and inform researchers as to which ER stress agent is appropriate with regards to their model.

show abstract

“…ER function is affected by various factors called ER stress, such as heat shock, cytotoxic chemicals, hypoxia, and inflammation, which lead to the disturbance of Ca 2+ homoeostasis and accumulation of unfolded proteins in the ER lumen (Ma and Hendershot, 2001;Kaufman et al, 2002). In autoimmune and inflammatory diseases, the ER activates the unfolded protein response (UPR) signaling pathways by protein folding, lipid and sterol biosynthesis, and storing intracellular Ca 2+ (Morito and Nagata, 2012). A class of ER stress proteins like members from heat shock proteins (HSPs) family serve as molecular chaperones and are induced in response to ER stress and then involved in protein folding and assembly (Kaufman, 1999).…”

Section: Introductionmentioning

confidence: 99%