5-LO inhibition ameliorates palmitic acid-induced ER stress, oxidative stress and insulin resistance via AMPK activation in murine myotubes

Kwak, Hyun Jeong; Choi, Hye Eun; Cheon, Hyae Gyeong

doi:10.1038/s41598-017-05346-5

Cited by 26 publications

(21 citation statements)

References 45 publications

(70 reference statements)

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“…It can induce IR in liver cells, skeletal muscles and cardiomyocytes, and plays an important role in the formation of diseases such as atherosclerosis and diabetes. [25][26][27] In this study, PA levels in GDM and PE patients showed an upward trend, and GDM were more prominent than PE patients. PA inhibits insulin-stimulated cellular glucose transport and increases blood glucose levels by attenuating tyrosine phosphorylation of the insulin receptor substrate and inhibiting the activation of phosphoinositide 3-kinase, which blocks insulin signaling.…”

Section: Fatty Acidssupporting

confidence: 48%

The application of metabolomics analysis in the research of gestational diabetes mellitus and preeclampsia

Teng

Zhang

et al. 2020

J of Obstet and Gynaecol

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Aim The aim of the study was to investigate the difference of the serum metabolic profile between gestational diabetes mellitus (GDM) patients and preeclampsia (PE) patients, to establish the disease differentiation model and to find characteristic metabolites, in order to provide a new idea for the occurrence, development and treatment of the disease. Methods Twenty‐nine patients with GDM group and 29 PE group who were examined in Tianjin No. 3 Central Hospital from March 2018 to August 2018 were enrolled as case group, and 29 normal pregnant women were selected as control group. All the serum samples were analyzed by using the ultra‐performance liquid chromatography and mass spectrometry. Based on the multivariate statistical analysis method of pattern recognition, we screened out and identified the differential characteristic metabolites. Results The serum metabolic profile model of GDM group and PE group was successfully constructed. A total of nine characteristic metabolites were screened and identified in this study, including LPC 18:0, LPC 22:6, LPC 16:0, (S)‐14‐methylhexadecanoic acid, behenic acid, palmitic acid, sphingosine, phytosphingosine and 1,25‐dihydroxyvitamin D3‐26,23‐lactone. Among them, six characteristic metabolites which were LPC 18:0, LPC 22:6, behenic acid, palmitic acid, sphingosine and 1,25‐dihydroxyvitamin D3‐26,23‐lactone all had a significant statistical difference among GDM, PE and normal pregnancy groups (P < 0.05). Conclusion The construction of metabolic profile discriminant model has a strong ability to differentiate GDM patients from PE pregnant women. The screened characteristic metabolites can early reflect the disorder of lipid, calcium and phosphorus metabolism of patients, and provide reference and help for the discussion of the occurrence, development and treatment of diseases.

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Section: Fatty Acidssupporting

confidence: 48%

The application of metabolomics analysis in the research of gestational diabetes mellitus and preeclampsia

Teng

Zhang

et al. 2020

J of Obstet and Gynaecol

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“…Recently, emerging evidences indicated that the ER stress pathway is another important pathway of inducing autophagy 37 , 38 . The endoplasmic reticulum is a large membrane-enclosed cellular organelle in eukaryotes to precede folding of membrane and secrete proteins.…”

Section: Discussionmentioning

confidence: 99%

“…The endoplasmic reticulum is a large membrane-enclosed cellular organelle in eukaryotes to precede folding of membrane and secrete proteins. Physiologic and pathological stresses such as aggregate-prone proteins, glucose deprivation, hypoxia, and efflux from the ER can lead to the failure of protein folding and then causing ER stress 37 , 39 . With the accumulation of unfolded proteins and damaged organelles during ER stress, autophagy can be activated by the unfolded protein response (UPR) 40 .…”

Section: Discussionmentioning

confidence: 99%

Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells

Zheng

Wang

et al. 2018

Sci Rep

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The aim of this study was to investigate the molecular mechanisms of the destruction of cytoskeletal structure by Zearalenone (ZEA) in mouse-derived TM4 cells. In order to investigate the role of autophagy, oxidative stress and endoplasmic reticulum(ER) stress in the process of destruction of cytoskeletal structure, the effects of ZEA on the cell viability, cytoskeletal structure, autophagy, oxidative stress, ER stress, MAPK and PI3K- AKT- mTOR signaling pathways were studied. The data demonstrated that ZEA damaged the cytoskeletal structure through the induction of autophagy that leads to the alteration of cytoskeletal structure via elevated oxidative stress. Our results further showed that the autophagy was stimulated by ZEA through PI3K-AKT-mTOR and MAPK signaling pathways in TM4 cells. In addition, ZEA also induced the ER stress which was involved in the induction of the autophagy through inhibiting the ERK signal pathway to suppress the phosphorylation of mTOR. ER stress was involved in the damage of cytoskeletal structure through induction of autophagy by producing ROS. Taken together, this study revealed that ZEA altered the cytoskeletal structure via oxidative stress - autophagy- ER stress pathway in mouse TM4 Sertoli cells.

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“…However, the MTT assay showed that PA reduced cell viability 24 h after treatment with 1,000 μM, compared to the non-treated cells. Other studies have also reported that PA reduced cell viability compared to non-treated cells at a concentration of 1,000 μM [14]. Therefore, ER stress was induced by using working concentrations of PA from 250 to 750 μM.…”

Section: Effect Of Pa and Emodin Treatment On Cell Viabilitymentioning

confidence: 92%

Emodin exerts protective effect against palmitic acid-induced endoplasmic reticulum stress in HepG2 cells

et al. 2019

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Purpose: Protein overloading in the endoplasmic reticulum (ER) leads to endoplasmic reticulum stress, which exacerbates various disease conditions. Emodin, an anthraquinone compound, is known to have several health benefits. The effect of emodin against palmitic acid (PA)-induced ER stress in HepG2 cells was investigated. Methods: HepG2 cells were treated with varying concentrations of palmitic acid to determine the working concentration that induced ER stress. ER stress associated genes such as ATF4, XBP1s, CHOP and GRP78 were checked using RT-PCR. In addition, the expression levels of unfolded protein response (UPR) associated proteins such as IRE1α, eIF2α and CHOP were checked using immunoblotting to confirm the induction of ER stress. The effect of emodin on ER stress was analyzed by treating HepG2 cells with 750 μM palmitic acid and varying concentrations of emodin, then analyzing the expression of UPR associated genes. Results: It was evident from the mRNA and protein expression results that palmitic acid significantly increased the expression of UPR associated genes and thereby induced ER stress. Subsequent treatment with emodin reduced the mRNA expression of ATF4, GRP78, and XBP1s. Furthermore, the protein levels of p-IRE1α, p-elF2α and CHOP were also reduced by the treatment of emodin. Analysis of sirtuin mRNA expression showed that emodin increased the levels of SIRT4 and SIRT7, indicating a possible role in decreasing the expression of UPR-related genes. Conclusion: Altogether, the results suggest that emodin could exert a protective effect against fatty acid-induced ER stress and could be an agent for the management of various ER stress related diseases.

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5-LO inhibition ameliorates palmitic acid-induced ER stress, oxidative stress and insulin resistance via AMPK activation in murine myotubes

Cited by 26 publications

References 45 publications

The application of metabolomics analysis in the research of gestational diabetes mellitus and preeclampsia

The application of metabolomics analysis in the research of gestational diabetes mellitus and preeclampsia

Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells

Emodin exerts protective effect against palmitic acid-induced endoplasmic reticulum stress in HepG2 cells

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