Impact of high cholesterol and endoplasmic reticulum stress on metabolic diseases: An updated mini-review

Sozen, Erdi; Özer, Nesrin Kartal

doi:10.1016/j.redox.2017.02.025

Cited by 155 publications

(105 citation statements)

References 69 publications

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“…Moreover, cholesterol production control occurs in the endoplasmic reticulum (ER). Thus, when the mechanism of cholesterol production is altered, it induces ER stress (Sozen and Ozer 2017).…”

Section: Discussionmentioning

confidence: 99%

Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles

et al. 2019

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Metal oxide nanoparticles (NPs), such as ZnO, ZnFe 2 O 4 , and Fe 2 O 3 , are widely used in industry. However, little is known about the cellular pathways involved in their potential toxicity. Here, we particularly investigated the key molecular pathways that are switched on after exposure to sub-toxic doses of ZnO, ZnFe 2 O 4 , and Fe 2 O 3 in the in vitro rat alveolar macrophages (NR8383). As in our model, the calculated IC 50 were respectively 16, 68, and more than 200 μg/mL for ZnO, ZnFe 2 O 4 , and Fe 2 O 3 ; global gene and protein expression profiles were only analyzed after exposure to ZnO and ZnFe 2 O 4 NPs. Using a rat genome microarray technology, we found that 985 and 1209 genes were significantly differentially expressed in NR8383 upon 4 h exposure to ¼ IC 50 of ZnO and ZnFe 2 O 4 NPs, respectively. It is noteworthy that metallothioneins were overexpressed genes following exposure to both NPs. Moreover, Ingenuity Pathway Analysis revealed that the top canonical pathway disturbed in NR8383 exposed to ZnO and ZnFe 2 O 4 NPs was eIF2 signaling involved in protein homeostasis. Quantitative mass spectrometry approach performed from both NR8383 cell extracts and culture supernatant indicated that 348 and 795 proteins were differentially expressed upon 24 h exposure to ¼ IC 50 of ZnO and ZnFe 2 O 4 NPs, respectively. Bioinformatics analysis revealed that the top canonical pathways disturbed in NR8383 were involved in protein homeostasis and cholesterol biosynthesis for both exposure conditions. While VEGF signaling was specific to ZnO exposure, iron homeostasis signaling pathway was specific to ZnFe 2 O 4 NPs. Overall, the study provides resource of transcriptional and proteomic markers of response to ZnO and ZnFe 2 O 4 NP-induced toxicity through combined transcriptomics, proteomics, and bioinformatics approaches.

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Section: Discussionmentioning

confidence: 99%

Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles

et al. 2019

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“…CH25H encodes the enzyme cholesterol 25 hydroxylase which converts cholesterol into the metabolite 25 hydroxycholesterol (25-HC). This metabolite has never previously been linked to marbling fat specifically but is certainly known as a potent regulator of cholesterol metabolism [23,24], fibroblastmediated tissue remodelling [25] and inflammation [26] all of which have been considered relevant to adiposity in various biological circumstances [27][28][29]. The tissue specific gene expression profile of CH25H in humans favours soft tissue (which includes adipose tissue) according to the TiGER gene expression database [30] supporting the possibility that adipose tissue may have a disproportionate influence over the systemic expression of this enzyme and its products.…”

Section: Imf Versus Sc Part III Ch25h and The 25 Hydroxylation Of Chomentioning

confidence: 99%

Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle

Hudson

Reverter²,

Griffiths

et al. 2020

BMC Genomics

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Background: This study used a genome-wide screen of gene expression to better understand the metabolic and functional differences between commercially valuable intramuscular fat (IMF) and commercially wasteful subcutaneous (SC) fat depots in Bos taurus beef cattle. Results: We confirmed many findings previously made at the biochemical level and made new discoveries. The fundamental lipogenic machinery, such as ACACA and FASN encoding the rate limiting Acetyl CoA carboxylase and Fatty Acid synthase were expressed at 1.6-1.8 fold lower levels in IMF, consistent with previous findings. The FA elongation pathway including the rate limiting ELOVL6 was also coordinately downregulated in IMF compared to SC as expected. A 2-fold lower expression in IMF of ACSS2 encoding Acetyl Coenzyme A synthetase is consistent with utilisation of less acetate for lipogenesis in IMF compared to SC as previously determined using radioisotope incorporation. Reduced saturation of fat in the SC depot is reflected by 2.4 fold higher expression of the SCD gene encoding the Δ9 desaturase enzyme. Surprisingly, CH25H encoding the cholesterol 25 hydroxylase enzyme was3 6 fold upregulated in IMF compared to SC. Moreover, its expression in whole muscle tissue appears representative of the proportional representation of bovine marbling adipocytes. This suite of observations prompted quantification of a set of oxysterols (oxidised forms of cholesterol) in the plasma of 8 cattle exhibiting varying IMF. Using Liquid Chromatography-Mass Spectrometry (LC-MS) we found the levels of several oxysterols were significantly associated with multiple marbling measurements across the musculature, but (with just one exception) no other carcass phenotypes. Conclusions: These data build on our molecular understanding of ruminant fat depot biology and suggest oxysterols represent a promising circulating biomarker for cattle marbling.

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“…Endoplasmic reticulum (ER) is an important intracellular organelle that is involved in protein translocation, 5 protein folding, and lipid biosynthesis. 6 Dysregulation of ER homeostasis through the ER-associated protein degradation pathway leads to ER stress and activation of the unfolded protein response. 7 Emerging studies indicate that ER stress response is associated with increased apoptosis in the placentas of patients with PE.…”

Section: Introductionmentioning

confidence: 99%

Hypermethylation of endoplasmic reticulum disulfide oxidase 1α leads to trophoblast cell apoptosis through endoplasmic reticulum stress in preeclampsia

Xiong

Ding

Gao

et al. 2018

J of Cellular Biochemistry

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Abnormal trophoblast cell apoptosis is implicated in the pathogenesis of pregnancy-related disorders including preeclampsia (PE), and endoplasmic reticulum (ER) stress has been considered as a novel pathway in the regulation of cell apoptosis. In this study, we observed that both apoptosis and ER stress are triggered in trophoblast cells under hypoxia as well as in the placenta of PE rats. Quantitative polymerase chain reaction and Western blot analysis showed that the expression of endoplasmic reticulum disulfide oxidase 1α (ERO1α) is suppressed in trophoblast cells under hypoxia due to the hypermethylation of the ERO1α promoter region, and the inhibition of ERO1α expression plays an important role in ER stress and trophoblast cell apoptosis. Furthermore, we found that DNA methyltransferase 1 (DNMT1) is a key methyltransferase for DNA methylation in the regulation of ERO1α expression, and the binding level of DNMT1 to the ERO1α promoter is markedly elevated under hypoxia although DNMT1 expression is inhibited by hypoxia, suggesting that the binding level of DNMT1 to the ERO1α promoter region rather than the DNMT1 expression level contributes to the hypermethylation of ERO1α. Taken together, these results demonstrate that the hypermethylation of ERO1α mediated by increased binding of DNMT1 to the ERO1α promoter leads to trophoblast cell apoptosis through ER stress in the placenta of PE rats, which shed insight into the etiology of PE and might present a validated therapeutic target for the treatment of PE.

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Impact of high cholesterol and endoplasmic reticulum stress on metabolic diseases: An updated mini-review

Cited by 155 publications

References 69 publications

Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles

Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles

Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle

Hypermethylation of endoplasmic reticulum disulfide oxidase 1α leads to trophoblast cell apoptosis through endoplasmic reticulum stress in preeclampsia

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