scholarly journals Endoplasmic Reticulum Stress-Related Factors Protect against Diabetic Retinopathy

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Wei-Kun Hu ◽  
Rong Liu ◽  
Han Pei ◽  
Bin Li
Keyword(s):  
Endoplasmic Reticulum ◽  
Diabetic Retinopathy ◽  
Er Stress ◽  
High Glucose ◽  
Expression Patterns ◽  
Protective Role ◽  
Normal Function ◽  
Future Research ◽  
Related Factors ◽  
Stress Related Genes

The endoplasmic reticulum (ER) is a principal mediator of signal transduction in the cell, and disruption of its normal function (a mechanism known as ER stress) has been associated with the pathogenesis of several diseases. ER stress has been demonstrated to contribute to onset and progression of diabetic retinopathy (DR) by induction of multiple inflammatory signaling pathways. Recent studies have begun to describe the gene expression profile of ER stress-related genes in DR; moreover, genes that play a protective role against DR have been identified.P58IPKwas determined to be able to reduce retinal vascular leakage under high glucose conditions, thus protecting retinal cells. It has also been found by our lab that ER-associated protein degradation factors exhibit significantly different expression patterns in rat retinas under sustained high glucose conditions. Future research based upon these collective genomic findings will contribute to our overall understanding of DR pathogenesis as well as identify potential therapeutic targets.

scholarly journals Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma

2021 ◽  
Author(s):  
Sinan Xiong ◽  
Wee-Joo Chng ◽  
Jianbiao Zhou
Keyword(s):  
Oxidative Stress ◽  
Multiple Myeloma ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cell Fate ◽  
Stress Responses ◽  
Plasma Cells ◽  
Reactive Oxygen Species Generation ◽  
Future Research ◽  
And Oxidative Stress

AbstractUnder physiological and pathological conditions, cells activate the unfolded protein response (UPR) to deal with the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum. Multiple myeloma (MM) is a hematological malignancy arising from immunoglobulin-secreting plasma cells. MM cells are subject to continual ER stress and highly dependent on the UPR signaling activation due to overproduction of paraproteins. Mounting evidence suggests the close linkage between ER stress and oxidative stress, demonstrated by overlapping signaling pathways and inter-organelle communication pivotal to cell fate decision. Imbalance of intracellular homeostasis can lead to deranged control of cellular functions and engage apoptosis due to mutual activation between ER stress and reactive oxygen species generation through a self-perpetuating cycle. Here, we present accumulating evidence showing the interactive roles of redox homeostasis and proteostasis in MM pathogenesis and drug resistance, which would be helpful in elucidating the still underdefined molecular pathways linking ER stress and oxidative stress in MM. Lastly, we highlight future research directions in the development of anti-myeloma therapy, focusing particularly on targeting redox signaling and ER stress responses.

scholarly journals Akebia trifoliate (Thunb.) KoidzSeed Extract Inhibits the Proliferation of Human Hepatocellular Carcinoma Cell Lines via Inducing Endoplasmic Reticulum Stress

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Wen-Li Lu ◽  
Hong-Yan Ren ◽  
Cao Liang ◽  
Yuan-Yuan Zhang ◽  
Ji Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Main Trend ◽  
G1 Phase ◽  
Cell Viability Assay ◽  
Cell Cycles ◽  
Viability Assay ◽  
M Phase ◽  
Stress Related Genes

Akebia Fructus has long been used for hepatocellular carcinoma (HCC) in China, while the molecular mechanism remains obscure. Our recent work found thatAkebia trifoliate (Thunb.) Koidzseed extract (ATSE) suppressed proliferation and induced endoplasmic reticulum (ER) stress in SMMC-7721. The present study aimed to throw more light on the mechanism. ER stress occurred after ATSE treatment in HepG2, HuH7, and SMMC-7721 cells, manifested as ER expansion, and SMMC-7721 was the most sensitive kind in terms of morphology. Cell viability assay showed that ATSE significantly inhibited cells proliferation. Flow cytometry analysis indicated that ATSE leads to an upward tendency of G0/G1 phase and a reduced trend of the continuous peak after G2/M phase in HepG2; ATSE promoted apoptosis in HuH7 and a notable reduction in G0/G1 phase; ATSE does not quite influence cell cycles of SMMC-7721. Western blot analysis showed an increased trend of the chosen ER stress-related proteins after different treatments but nonsignificantly; only HYOU1 and GRP78 were decreased notably by ATSE in HuH7. Affymetrix array indicated that lots of ER stress-related genes’ expressions were significantly altered, and downward is the main trend. These results suggest that ATSE have anticancer potency in HCC cells via partly inducing ER stress.

scholarly journals Expression of Endoplasmic Reticulum Stress-Related Factors in the Retinas of Diabetic Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Shu Yan ◽  
Cui Zheng ◽  
Zhi-qi Chen ◽  
Rong Liu ◽  
Gui-gang Li ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Western Blot ◽  
Er Stress ◽  
Diabetic Rats ◽  
Stress Factors ◽  
Diabetic Rat ◽  
Related Factors ◽  
Diabetes Model ◽  
Polymerase Chain

Recent reports show that ER stress plays an important role in diabetic retinopathy (DR), but ER stress is a complicated process involving a network of signaling pathways and hundreds of factors, What factors involved in DR are not yet understood. We selected 89 ER stress factors from more than 200, A rat diabetes model was established by intraperitoneal injection of streptozotocin (STZ). The expression of 89 ER stress-related factors was found in the retinas of diabetic rats, at both 1- and 3-months after development of diabetes, by quantitative real-time polymerase chain reaction arrays. There were significant changes in expression levels of 13 and 12 ER stress-related factors in the diabetic rat retinas in the first and third month after the development of diabetes, Based on the array results, homocysteine- inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1(HERP), and synoviolin(HRD1) were studied further by immunofluorescence and Western blot. Immunofluorescence and Western blot analyses showed that the expression of HERP was reduced in the retinas of diabetic rats in first and third month. The expression of Hrd1 did not change significantly in the retinas of diabetic rats in the first month but was reduced in the third month.

scholarly journals Modulation of the Physical Properties of 3D Spheroids Derived from Human Scleral Stroma Fibroblasts (HSSFs) with Different Axial Lengths Obtained from Surgical Patients

2021 ◽  
Vol 43 (3) ◽  
pp. 1715-1725
Author(s):  
Hiroyasu Katayama ◽  
Masato Furuhashi ◽  
Araya Umetsu ◽  
Fumihito Hikage ◽  
Megumi Watanabe ◽  
...  
Keyword(s):  
Physical Properties ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Lysyl Oxidase ◽  
Hypoxia Inducible Factor ◽  
Three Dimensional ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Down Regulation ◽  
Related Factors ◽  
Stress Related Genes

In the current study, to elucidate the pathological characteristics of myopic scleral stroma, three-dimensional (3D) cultures of human scleral stroma fibroblasts (HSSFs) with several axial lengths (AL, 22.80–30.63 mm) that were obtained from patients (n = 7) were examined. Among the three groups of ALs, <25 mm (n = 2), 25–30 mm (n = 2), and >30 mm (n = 3), the physical properties of the 3D HSSFs spheroids with respect to size and stiffness, the expressions of extracellular matrix (ECM) molecules, including collagen (COL) 1, 4, and 6 and fibronectin (FN) by qPCR and immunohistochemistry (IHC), and the mRNA expression of ECM metabolism modulators including hypoxia-inducible factor 1A (HIF 1A), HIF 2A, lysyl oxidase (LOX), tissue inhibitor of metalloproteinase (TIMP) 1–4, and matrix metalloproteinase (MMP) 2, 9, and 14 as well as several endoplasmic reticulum (ER) stress-related factors were compared. In the largest AL group (>30 mm), the 3D HSSFs spheroids were (1) significantly down-sized and less stiff compared to the other groups, and (2) significant changes were detected in the expression of some ECMs (qPCR; the up-regulation of COL1 and COL4, and the down-regulation of FN, IHC; the up-regulation of COL1 and FN, and down-regulation of COL4). The mRNA expressions of ECM modulators and ER stress-related genes were also altered with increasing AL length (up-regulation of HIF2A, MMP2, XBP1, and MMP14, down-regulation of LOX, TIMP 2 and 3, GRP78, GRP94, IRE1, and ATF6). In addition, a substantial down-regulation of some ER stress-related genes (ATF4, sXPB1 and CHOP) was observed in the 25–30 mm AL group. The findings presented herein suggest that small and stiffer 3D HSSFs spheroids in the largest AL group may accurately replicate the pathological significance of scleral thinning and weakening in myopic eyes. In addition, the modulation of several related factors among the different AL groups may also provide significant insights into our understanding of the molecular mechanisms responsible for causing myopic changes in the sclera.

scholarly journals Endoplasmic Reticulum Stress Induced Proliferation Remains Intact in Aging Mouse β-Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Jarin T. Snyder ◽  
Christine Darko ◽  
Rohit B. Sharma ◽  
Laura C. Alonso
Keyword(s):  
Cell Proliferation ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
High Glucose ◽  
Low Dose ◽  
Target Genes ◽  
Brdu Incorporation ◽  
Older Individuals ◽  
Β Cells ◽  
Β Cell

Aging is associated with loss of proliferation of the insulin-secreting β-cell, a possible contributing factor to the increased prevalence of type 2 diabetes in the elderly. Our group previously discovered that moderate endoplasmic reticulum (ER) stress occurring during glucose exposure increases the adaptive β-cell proliferation response. Specifically, the ATF6α arm of the tripartite Unfolded Protein Response (UPR) promotes β-cell replication in glucose excess conditions. We hypothesized that β-cells from older mice have reduced proliferation due to aberrant UPR signaling or an impaired proliferative response to ER stress or ATF6α activation. To investigate, young and old mouse islet cells were exposed to high glucose with low-dose thapsigargin or activation of overexpressed ATF6α, and β-cell proliferation was quantified by BrdU incorporation. UPR pathway activation was compared by qPCR of target genes and semi-quantitative Xbp1 splicing assay. Intriguingly, although old β-cells had reduced proliferation in high glucose compared to young β-cells, UPR activation and induction of proliferation in response to low-dose thapsigargin or ATF6α activation in high glucose were largely similar between young and old. These results suggest that loss of UPR-led adaptive proliferation does not explain the reduced cell cycle entry in old β-cells, and raise the exciting possibility that future therapies that engage adaptive UPR could increase β-cell number through proliferation even in older individuals.

scholarly journals Exploring the Differential Gene of CHOP-Related Factors in Hepatocellular Injury Caused by Endoplasmic Reticulum Stress

2021 ◽  
Author(s):  
Leng-xin Duan ◽  
Man-lin Guo ◽  
Xiang-yu Ma ◽  
Yu-qing Gong ◽  
San-qiang Li
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Cell Receptor ◽  
Differentially Expressed ◽  
Lipocalin 2 ◽  
Hepatocellular Injury ◽  
Chromosome 11 ◽  
Gamma Chain ◽  
Related Factors

Abstract Objective: CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP/DDIT3) is a protein activated by endoplasmic reticulum stress (ERS). However, the downstream genes of CHOP on liver damage caused by ER-stress have been unclear. Herein, we investigated the potential downstream related factors of CHOP in L-02 cells.Methods and Material: Tunicamycin (TM) was used to induce ER-stress. Short hairpin RNA (shRNA) was used to knocked down CHOP, and the functions of differentially expressed genes (DEGs) were obtained from functional annotations. qRT-PCR was employed to validate the expression levels of candidate DEGs.Results: 633 genes were differentially expressed between ERS L-02 cells and normal L-02 cells，and 131 genes were differentially expressed between shRNA-CHOP and shRNA-NC in ERS L-02 cells. By analyze these results, we luckily found 8 genes including Interferon a-inducible protein 27 (IFI27), Lipocalin 2 (LCN2), Chromosome 11 Open Reading Frame 86 (C11orf86), Calmegin (CLGN), Kelch domain- containing 7B (KLHDC7B), Niban Apoptosis Regulator 1 (Niban), T-Cell Receptor Gamma- Chain Constant Region (TARP), Lysosome associated membrane protein 3 (LAMP3) were intimately related to chop. Conclusion: Our study might contribute to better understand how CHOP functions during ER-stress, and these results can expand databases of CHOP in GenBank or others.

scholarly journals Analysis of the transcriptome and DNA methylome in response to acute and recurrent low glucose in human primary astrocytes

2020 ◽  
Author(s):  
Paul G Weightman Potter ◽  
Sam Washer ◽  
Aaron R Jeffries ◽  
Janet E Holley ◽  
Nick J Gutowski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Dna And Rna ◽  
Human Astrocytes ◽  
Low Glucose ◽  
Primary Astrocytes ◽  
Stress Related Genes ◽  
Pathway Analyses ◽  
The Unfolded Protein Response

ABSTRACTAims/hypothesisRecurrent hypoglycaemia (RH) is a major side-effect of intensive insulin therapy for people with diabetes. Changes in hypoglycaemia sensing by the brain contribute to the development of impaired counterregulatory responses to and awareness of hypoglycaemia. Little is known about the intrinsic changes in human astrocytes in response to acute and recurrent low glucose (RLG) exposure.MethodsHuman primary astrocytes (HPA) were exposed to zero, one, three or four bouts of low glucose (0.1 mmol/l) for three hours per day for four days to mimic RH. On the fourth day, DNA and RNA were collected. Differential gene expression and ontology analyses were performed using DESeq2 and GOseq respectively. DNA methylation was assessed using the Infinium MethylationEPIC BeadChip platform.Results24 differentially expressed genes (DEGs) were detected (after correction for multiple comparisons). One bout of low glucose exposure had the largest effect on gene expression. Pathway analyses revealed that endoplasmic-reticulum (ER) stress-related genes such as HSPA5, XBP1, and MANF, involved in the unfolded protein response (UPR), were all significantly increased following LG exposure, which was diminished following RLG. There was little correlation between differentially methylated positions and changes in gene expression yet the number of bouts of LG exposure produced distinct methylation signatures.Conclusions/interpretationThese data suggest that exposure of human astrocytes to transient LG triggers activation of genes involved in the UPR linked to endoplasmic reticulum (ER) stress. Following RLG, the activation of UPR related genes was diminished, suggesting attenuated ER stress. This may be mediated by metabolic adaptations to better preserve intracellular and/or ER ATP levels, but this requires further investigation.

scholarly journals Seipin Deficiency Accelerates Heart Failure Due to Calcium Handling Abnormalities and Endoplasmic Reticulum Stress in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaoyue Wu ◽  
Xuejing Liu ◽  
Huan Wang ◽  
Zihao Zhou ◽  
Chengzhi Yang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Endoplasmic Reticulum ◽  
Cardiac Hypertrophy ◽  
Er Stress ◽  
Diastolic Heart Failure ◽  
Left Ventricular ◽  
Calcium Handling ◽  
Related Factors ◽  
Current Decay ◽  
Protein Levels

Seipin deficiency can induce hypertrophic cardiomyopathy and heart failure, which often leads to death in humans. To explore the effects and the possible mechanisms of Seipin deficiency in myocardial remodeling, Seipin knockout (SKO) mice underwent transverse aortic constriction (TAC) for 12 weeks. We found a more severe left ventricular hypertrophy and diastolic heart failure and increases in inflammatory cell infiltration, collagen deposition, and apoptotic bodies in the SKO group compared to those in the wild type (WT) group after TAC. Electron microscopy also showed a more extensive sarcoplasmic reticulum expansion, deformation of microtubules, and formation of mitochondrial lesions in the cardiomyocytes of SKO mice than in those of WT mice after TAC. Compared with the WT group, the SKO group showed increases in endoplasmic reticulum (ER) stress-, inflammation-, and fibrosis-related gene expression, while calcium ion-related factors, such as Serca2a and Ryr, were decreased in the SKO group after TAC. Increased levels of the ER stress-related protein GRP78 and decreased SERCA2a and P-RYR protein levels were detected in the SKO group compared with the WT group after TAC. Slowing of transient Ca2+ current decay and an increased SR Ca2+ content in myocytes were detected in the cardiomyocytes of SKO mice. Adipose tissue transplantation could not rescue the cardiac hypertrophy after TAC in SKO mice. In conclusion, we found that Seipin deficiency could promote cardiac hypertrophy and diastolic heart failure after TAC in mice. These changes may be related to the impairment of myocardial calcium handling, ER stress, inflammation, and apoptosis.

scholarly journals AdipoRon Protects against Tubular Injury in Diabetic Nephropathy by Inhibiting Endoplasmic Reticulum Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Shan Xiong ◽  
Yachun Han ◽  
Peng Gao ◽  
Hao Zhao ◽  
Na Jiang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Diabetic Nephropathy ◽  
Er Stress ◽  
High Glucose ◽  
Underlying Mechanism ◽  
Adiponectin Receptor ◽  
Tubular Injury ◽  
Beneficial Effects ◽  
Compound C

Endoplasmic reticulum (ER) stress has been reported to play a pivotal role in diabetic nephropathy (DN). AdipoRon is a newly developed adiponectin receptor agonist that provides beneficial effects for diabetic mice; however, its underlying mechanism remains to be delineated. Here, we demonstrated increased expression levels of ER stress markers, accompanied by upregulated levels of proinflammatory cytokines and increased expression of collagen I, fibronectin, Bax, and cleaved caspase 3 in the kidneys of db/db mice compared with control mice. Decreased expression of adiponectin receptor 1 (AdipoR1) and phosphorylated 5′AMP-activated kinase (p-AMPK) was also observed in the kidneys of db/db mice. However, these alterations were partially reversed by intragastric gavage with AdipoRon. In vitro, AdipoRon alleviated high-glucose-induced ER stress, oxidative stress, and apoptosis in HK-2 cells, a human tubular cell line. Moreover, AdipoRon restored the expression of AdipoR1 and p-AMPK in HK-2 cells exposed to high-glucose conditions. Additionally, these effects were partially abrogated by pretreatment with AdipoR1 siRNA, but this abrogation was ameliorated by cotreatment with AICAR, an AMPK activator. Furthermore, the effects of AdipoRon were also partially abolished by cotreatment with compound C. Together, these results suggest that AdipoRon exerts favorable effects on diabetes-induced tubular injury in DN by inhibiting ER stress mediated by the AdipoR1/p-AMPK pathway.

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