Enhanced endoplasmic reticulum SERCA activity by overexpression of hepatic stimulator substance gene prevents hepatic cells from ER stress-induced apoptosis

Zhang, Jing; Li, Yuan; Jiang, Shujun; Yu, Honggang; An, Wei

doi:10.1152/ajpcell.00117.2013

Cited by 66 publications

(47 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…www.impactjournals.com/oncotarget (PI3K) inhibitor, was used to block autophagy because the complex of Beclin-1 and PI3K is required for autophagic vesicle nucleation [17]. As reported in a previous study [18][19][20][21], less apoptotic cells were observed in mice treated with CCl 4 and ALR than those treated with CCl 4 only, which suggested that ALR inhibits hepatocyte apoptosis. 3-MA addition significantly promoted cell apoptosis in mice treated with CCl 4 and ALR, which indicated the inhibition of autophagy reverses the anti-apoptotic effect of ALR in acute liver injury ( Figure 5).…”

Section: Alr Suppresses Hepatocyte Apoptosis In Mice With CCL 4 -Indumentioning

confidence: 83%

Augmenter of liver regeneration protects against carbon tetrachloride-induced liver injury by promoting the autophagy in mice

Han¹,

Shi²,

Duan³

2017

Journal of Hepatology

View full text Add to dashboard Cite

Section: Alr Suppresses Hepatocyte Apoptosis In Mice With CCL 4 -Indumentioning

confidence: 83%

Augmenter of liver regeneration protects against carbon tetrachloride-induced liver injury by promoting the autophagy in mice

Han¹,

Shi²,

Duan³

2017

Journal of Hepatology

View full text Add to dashboard Cite

“…Increased PC/PE ratio of the ER membrane leads to altered membrane fluidity which reduces SERCA2b function, resulting in decreased Ca 2+ accumulation in the ER lumen and impaired protein folding capacity (Fu et al, 2011). Similarly, two independent groups have recently shown that the incorporation of saturated fatty acids into the ER also reduces membrane fluidity and SERCA function, decreasing luminal ER Ca 2+ (Egnatchik et al, 2014; Zhang et al, 2014b). It has also been shown that modulation of LXRs regulates ER function through changes in membrane phospholipid composition and lipogenic and inflammatory responses (Rong et al, 2013).…”

Section: Liver Metabolism Function and Ca2+ Homeostasismentioning

confidence: 93%

Calcium Homeostasis and Organelle Function in the Pathogenesis of Obesity and Diabetes

2015

View full text Add to dashboard Cite

Summary A number of chronic metabolic pathologies, including obesity, diabetes, cardiovascular disease, asthma, and cancer cluster together to present the greatest threat to human health. As research in this field has advanced, it has become clear that unresolved metabolic inflammation, organelle dysfunction, and other cellular and metabolic stresses underlie the development of these chronic metabolic diseases. However, the relationship between these systems and pathological mechanisms is poorly understood. Here, we will discuss the role of cellular Ca2+ homeostasis as a critical mechanism integrating the myriad of cellular and subcellular dysfunctional networks found in metabolic tissues such as liver and adipose tissue in the context of metabolic disease particularly in obesity and diabetes.

show abstract

“…Studies of cultured hepatocytes and hepatocellular carcinoma lines have revealed that exposure to excess saturated fatty acids in particular triggers cellular stress responses that can lead to cell death [9][10][11][12][13][14][15][16][17][18][19]. For these experiments, cells are typically incubated with palmitate (0.2 to 1.0 mM) conjugated to bovine serum albumin (BSA).…”

Section: Introductionmentioning

confidence: 99%

Differential Lipotoxic Effects of Palmitate and Oleate in Activated Human Hepatic Stellate Cells and Epithelial Hepatoma Cells

Hetherington

Sawyez²,

Zilberman³

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) progression to fibrosis, cirrhosis and hepatocellular carcinoma, alters the cellular composition of this organ. During late-stage NAFLD, fibrotic and possibly cancerous cells can proliferate and, like normal hepatocytes, are exposed to high concentrations of fatty acids from both surrounding tissue and circulating lipid sources. We hypothesized that primary human activated hepatic stellate cells and epithelial hepatoma (HepG2) cells respond differently to lipotoxic conditions, and investigated the mechanisms involved. Methods: Primary activated hepatic stellate cells and HepG2 cells were exposed to pathophysiological concentrations of fatty acids and comparative studies of lipid metabolic and stress response pathways were performed. Results: Both cell types remained proliferative during exposure to a combination of palmitate plus oleate reflective of the general saturated versus unsaturated fatty acid composition of western diets. However, exposure to either high palmitate or high oleate alone induced cytotoxicity in activated stellate cells, while only palmitate caused cytotoxicity in HepG2 cells. mRNA microarray and biochemical comparisons revealed that stellate cells stored markedly less fatty acids as neutral lipids, and had reduced capacity for beta-oxidation. Similar to previous observations in HepG2 cells, palmitate, but not oleate, induced ER stress and actin stress fiber formation in activated stellate cells. In contrast, oleate, but not palmitate, induced the inflammatory signal TXNIP, decreased cytoskeleton proteins, and decreased cell polarity preceding cell death in activated stellate cells. Conclusions: Palmitate-induced lipotoxicity was associated with ER stress pathways in both primary activated hepatic stellate cells and epithelial hepatoma cells, whereas high oleate caused lipotoxicity only in activated stellate cells, possibly through a distinct mechanism involving disruption of cytoskeleton components. This may have implications for optimal dietary fatty acid compositions during various stages of NAFLD.

show abstract

Enhanced endoplasmic reticulum SERCA activity by overexpression of hepatic stimulator substance gene prevents hepatic cells from ER stress-induced apoptosis

Abstract: An W. Enhanced endoplasmic reticulum SERCA activity by overexpression of hepatic stimulator substance gene prevents hepatic cells from ER stress-induced apoptosis.

Cited by 66 publications

References 57 publications

Augmenter of liver regeneration protects against carbon tetrachloride-induced liver injury by promoting the autophagy in mice

Augmenter of liver regeneration protects against carbon tetrachloride-induced liver injury by promoting the autophagy in mice

Calcium Homeostasis and Organelle Function in the Pathogenesis of Obesity and Diabetes

Differential Lipotoxic Effects of Palmitate and Oleate in Activated Human Hepatic Stellate Cells and Epithelial Hepatoma Cells

Contact Info

Product

Resources

About