Ixeris dentata Decreases ER Stress and Hepatic Lipid Accumulation through Regulation of ApoB Secretion

2014 ◽  
Vol 42 (03) ◽  
pp. 639-649 ◽  
Author(s):  
Mi-Rin Lee ◽  
Hwa-Young Lee ◽  
Geum-Hwa Lee ◽  
Hye-Kyung Kim ◽  
Nan-Young Kim ◽  
...  
Keyword(s):  
Stress Response ◽  
Er Stress ◽  
Lipid Accumulation ◽  
Herbal Remedy ◽  
Saturated Fatty Acids ◽  
Initiation Factor ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Er Stress Response ◽  
Ixeris Dentata

Nonalcoholic fatty liver disease (NAFLD) is caused by the hepatic accumulation of saturated fatty acids involving the ER stress mechanism. Secretion of apo lipid carrier proteins and their binding to hepatic TG and cholesterol are affected by ER stress. This study was designed to identify ER stress regulators with potential effects against hepatic lipid accumulation. Ixeris dentata (IXD) is a traditional herbal remedy for indigestion, hepatitis, and diabetes used in Korea, Japan, and China. To examine the regulatory effects of IXD against hepatic lipid accumulation and elucidate its suggested mechanism of ER stress, HepG2 hepatocytes were treated with IXD extract in the presence of palmitate. While palmitate induced an ER stress response in hepatocytes, as indicated by the upregulation of PERK, increased eukaryotic initiation factor 2α (eIF2α) phosphorylation, enhanced expression of GADD153/C/EBP homologous protein (CHOP), and reduced secretion of apoB resulting in hepatic cellular accumulation of triglycerides (TG) and cholesterol, IXD extract significantly inhibited the lipid accumulation and PERK/eIF2α/CHOP-axis of the ER stress response. The inhibition of the PERK/eIF2α/CHOP signaling pathway by IXD in palmitate-treated cells suggests that IXD regulates hepatic dyslipidemia through the regulation of ER stress.

scholarly journals Mechanism of the Inhibitory Effects ofEucommia ulmoidesOliv. Cortex Extracts (EUCE) in the CCl4-Induced Acute Liver Lipid Accumulation in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Chang-Feng Jin ◽  
Bo Li ◽  
Shun-Mei Lin ◽  
Raj-Kumar Yadav ◽  
Hyung-Ryong Kim ◽  
...  
Keyword(s):  
Er Stress ◽  
Lipid Accumulation ◽  
Liver Lipid ◽  
Eucommia Ulmoides ◽  
Dependent Manner ◽  
Protective Effects ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Er Stress Response ◽  
Acute Injection

Eucommia ulmoidesOliv. (EU) has been used for treatment of liver diseases. The protective effects ofEucommia UlmoidesOliv. cortex extracts (EUCE) on the carbon tetrachloride- (CCl4-) induced hepatic lipid accumulation were examined in this study. Rats were orally treated with EUCE in different doses prior to an intraperitoneal injection of 1 mg/kg CCl4. Acute injection of CCl4decreased plasma triglyceride but increased hepatic triglyceride and cholesterol as compared to control rats. On the other hand, the pretreatment with EUCE diminished these effects at a dose-dependent manner. CCl4treatment decreased glutathione (GSH) and increased malondialdehyde (MDA) accompanied by activated P450 2E1. The pretreatment with EUCE significantly improved these deleterious effects of CCl4. CCl4treatment increased P450 2E1 activation and ApoB accumulation. Pretreatment with EUCE reversed these effects. ER stress response was significantly increased by CCl4, which was inhibited by EUCE. One of the possible ER stress regulatory mechanisms, lysosomal activity, was examined. CCl4reduced lysosomal enzymes that were reversed with the EUCE. The results indicate that oral pretreatment with EUCE may protect liver against CCl4-induced hepatic lipid accumulation. ER stress and its related ROS regulation are suggested as a possible mechanism in the antidyslipidemic effect of EUCE.

scholarly journals Salubrinal, an inhibitor of protein synthesis, promotes deep slow wave sleep

2009 ◽  
Vol 296 (1) ◽  
pp. R178-R184 ◽  
Author(s):  
Melvi M. Methippara ◽  
Tariq Bashir ◽  
Sunil Kumar ◽  
Noor Alam ◽  
Ronald Szymusiak ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Stress Response ◽  
Er Stress ◽  
Slow Wave ◽  
Slow Wave Sleep ◽  
Nrem Sleep ◽  
Initiation Factor ◽  
Er Stress Response ◽  
Intracerebroventricular Infusion ◽  
Inhibitor Of Protein Synthesis

Previous work showed that sleep is associated with increased brain protein synthesis and that arrest of protein synthesis facilitates sleep. Arrest of protein synthesis is induced during the endoplasmic reticulum (ER) stress response, through phosphorylation of eukaryotic initiation factor 2α (p-eIF2α). We tested a hypothesis that elevation of p-eIF2α would facilitate sleep. We studied the effects of intracerebroventricular infusion of salubrinal (Salub), which increases p-eIF2α by inhibiting its dephosphorylation. Salub increased deep slow wave sleep by 255%, while reducing active waking by 49%. Delta power within non-rapid eye movement (NREM) sleep was increased, while power in the sigma, beta, and gamma bands during NREM was reduced. We found that Salub increased expression of p-eIF2α in the basal forebrain (BF) area, a sleep-wake regulatory brain region. Therefore, we quantified the p-eIF2α-immunolabeled neurons in the BF area; Salub administration increased the number of p-eIF2α-expressing noncholinergic neurons in the caudal BF. In addition, Salub also increased the intensity of p-eIF2α expression in both cholinergic and noncholinergic neurons, but this was more widespread among the noncholinergic neurons. Our findings support a hypothesis that sleep is facilitated by signals associated with the ER stress response.

scholarly journals Caffeine reduces hepatic lipid accumulation through regulation of lipogenesis and ER stress in zebrafish larvae

2015 ◽  
Vol 22 (1) ◽  
Author(s):  
Xinchun Zheng ◽  
Wencong Dai ◽  
Xiaohui Chen ◽  
Kunyuan Wang ◽  
Wenqing Zhang ◽  
...  
Keyword(s):  
Er Stress ◽  
Lipid Accumulation ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Zebrafish Larvae

scholarly journals Fisetin Protects HaCaT Human Keratinocytes from Fine Particulate Matter (PM2.5)-Induced Oxidative Stress and Apoptosis by Inhibiting the Endoplasmic Reticulum Stress Response

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1492
Author(s):  
Ilandarage Menu Neelaka Molagoda ◽  
Mirissa Hewage Dumindu Kavinda ◽  
Yung Hyun Choi ◽  
Hyesook Lee ◽  
Chang-Hee Kang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Particulate Matter ◽  
Stress Response ◽  
Er Stress ◽  
Fine Particulate Matter ◽  
Human Keratinocytes ◽  
Initiation Factor ◽  
Er Stress Response ◽  
Fine Particulate ◽  
Induced Apoptosis

Fine particulate matter (PM2.5) originates from the combustion of coal and is found in the exhaust of fumes of diesel vehicles. PM2.5 readily penetrates the skin via the aryl hydrocarbon receptor, causing skin senescence, inflammatory skin diseases, DNA damage, and carcinogenesis. In this study, we investigated whether fisetin, a bioactive flavonoid, prevents PM2.5-induced apoptosis in HaCaT human keratinocytes. The results demonstrated that fisetin significantly downregulated PM2.5-induced apoptosis at concentrations below 10 μM. Fisetin strongly inhibited the production of reactive oxygen species (ROS) and the expression of pro-apoptotic proteins. The PM2.5-induced apoptosis was associated with the induction of the endoplasmic reticulum (ER) stress response, mediated via the protein kinase R-like ER kinase (PERK)–eukaryotic initiation factor 2α (eIF2α)–activating transcription factor 4 (ATF4)–CCAAT-enhancer-binding protein (C/EBP) homologous protein (CHOP) axis. Additionally, the cytosolic Ca2+ levels were markedly increased following exposure to PM2.5. However, fisetin inhibited the expression of ER stress-related proteins, including 78 kDa glucose-regulated protein (GRP78), phospho-eIF2α, ATF4, and CHOP, and reduced the cytosolic Ca2+ levels. These data suggest that fisetin inhibits PM2.5-induced apoptosis by inhibiting the ER stress response and production of ROS.

scholarly journals Eucommia ulmoides Oliver Extract, Aucubin, and Geniposide Enhance Lysosomal Activity to Regulate ER Stress and Hepatic Lipid Accumulation

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e81349 ◽  
Author(s):  
Hwa-Young Lee ◽  
Geum-Hwa Lee ◽  
Mi-Rin Lee ◽  
Hye-Kyung Kim ◽  
Nan-young Kim ◽  
...  
Keyword(s):  
Er Stress ◽  
Lipid Accumulation ◽  
Eucommia Ulmoides ◽  
Lysosomal Activity ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Eucommia Ulmoides Oliver

scholarly journals Endoplasmic reticulum stress in glomerular epithelial cell injury

2011 ◽  
Vol 301 (3) ◽  
pp. F496-F508 ◽  
Author(s):  
Andrey V. Cybulsky ◽  
Tomoko Takano ◽  
Joan Papillon ◽  
Thomas M. Kitzler ◽  
Krikor Bijian
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Epithelial Cell ◽  
Er Stress ◽  
Cell Injury ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Glomerular Epithelial Cell ◽  
Er Stress Response

Focal segmental glomerulosclerosis (FSGS) may be associated with glomerular epithelial cell (GEC; podocyte) apoptosis due to acquired injury or mutations in specific podocyte proteins. This study addresses mediation of GEC injury, focusing on endoplasmic reticulum (ER) stress. We studied signaling in cultured GECs in the presence or absence of the extracellular matrix (ECM). Adhesion to collagen supports cell survival, but adhesion to plastic (loss of contact with ECM) leads to apoptosis. Compared with collagen-adherent cells, GECs on plastic showed increased protein misfolding in the ER, and an adaptive-protective ER stress response, including increased expression of ER chaperones, increased phosphorylation of eukaryotic translation initiation factor-2α (eIF2α), and a reduction in protein synthesis. Activation of these ER stress pathways counteracted apoptosis. However, tunicamycin (a potent stimulator of ER stress) changed the ER stress response from protective to cytotoxic, as tunicamycin induced the proapoptotic ER stress gene, C/EBP homologous protein-10, and exacerbated apoptosis in GECs adherent to plastic, but not collagen. In GECs adherent to plastic, adaptive ER stress was associated with an increase in polyubiquitinated proteins and “choking” of the proteasome. Furthermore, pharmacological inhibition of the proteasome induced ER stress in GECs. Finally, we show that ER stress (induction of ER chaperones and eIF2α phosphorylation) was evident in experimental FSGS in vivo. Thus interactions of GECs with ECM may regulate protein folding and induction of the ER stress response. FSGS is associated with induction of ER stress. Enhancing protective aspects of the ER stress response may reduce apoptosis and possibly glomerulosclerosis.

scholarly journals Herpes Simplex Virus 1 Infection Activates the Endoplasmic Reticulum Resident Kinase PERK and Mediates eIF-2α Dephosphorylation by the γ134.5 Protein

2005 ◽  
Vol 79 (3) ◽  
pp. 1379-1388 ◽  
Author(s):  
Guofeng Cheng ◽  
Zongdi Feng ◽  
Bin He
Keyword(s):  
Endoplasmic Reticulum ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Stress Response ◽  
Er Stress ◽  
Translation Initiation Factor ◽  
Productive Infection ◽  
Initiation Factor ◽  
Er Stress Response ◽  
Simplex Virus

ABSTRACT The γ134.5 protein of herpes simplex virus (HSV) plays a crucial role in virus infection. Although the double-stranded RNA-dependent protein kinase (PKR) is activated during HSV infection, the γ134.5 protein inhibits the activity of PKR by mediating dephosphorylation of the translation initiation factor eIF-2α. Here we show that HSV infection also induces phosphorylation of an endoplasmic reticulum (ER) resident kinase PERK, a hallmark of ER stress response. The virus-induced phosphorylation of PERK is blocked by cycloheximide but not by phosphonoacetic acid, suggesting that the accumulation of viral proteins in the ER is essential. Notably, the maximal phosphorylation of PERK is delayed in PKR+/+ cells compared to that seen in PKR−/− cells. Further analysis indicates that hyperphosphorylation of eIF-2α caused by HSV is greater in PKR+/+ cells than in PKR−/− cells. However, expression of the γ134.5 protein suppresses the ER stress response caused by virus, dithiothreitol, and thapsigargin as measured by global protein synthesis. Interestingly, the expression of GADD34 stimulated by HSV infection parallels the status of eIF-2α phosphorylation. Together, these observations suggest that regulation of eIF-2α phosphorylation by the γ134.5 protein is an efficient way to antagonize the inhibitory activity of PKR as well as PERK during productive infection.

Differential regulation of the ER stress response by long-chain fatty acids in the pancreatic β-cell

2008 ◽  
Vol 36 (5) ◽  
pp. 959-962 ◽  
Author(s):  
Eleftheria Diakogiannaki ◽  
Noel G. Morgan
Keyword(s):  
Fatty Acids ◽  
Stress Response ◽  
Er Stress ◽  
Unsaturated Fatty Acids ◽  
Initiation Factor ◽  
Long Chain Fatty Acids ◽  
Β Cells ◽  
Er Stress Response ◽  
Long Chain ◽  
Chain Fatty Acids

Recent evidence indicates that treatment of pancreatic β-cells with long chain fatty acids can lead to the development of an ER (endoplasmic reticulum) stress response. This is manifest as the activation of some components of the PERK [RNA-dependent protein kinase-like ER eIF2α (eukaryotic initiation factor 2α) kinase]-dependent arm of ER stress and is seen most dramatically when cells are treated with long-chain saturated fatty acids (e.g. palmitate). By contrast, the equivalent mono-unsaturates (e.g. palmitoleate) are much less effective and they can even attenuate the ER stress response to palmitate. This may be due to the regulation of eIF2α phosphorylation in cells exposed to mono-unsaturates. The present review discusses the differential effects of saturated and mono-unsaturated fatty acids on ER stress in β-cells and considers the extent to which regulation of this pathway may be involved in mediating their effects on viability.

Sign in / Sign up

Export Citation Format

Share Document