Baicalein protects rat insulinoma INS-1 cells from palmitate-induced lipotoxicity by inducing HO-1

Kwak, Hyun Jeong; Yang, Dongki; Hwang, Yongha; Lee, Youn-Jung; Cheon, Hyae Gyeong

doi:10.1371/journal.pone.0176432

Cited by 29 publications

(20 citation statements)

References 39 publications

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“…The neuroprotective effects could be attributed to NF-κB inhibition and nuclear factor E2-related factor 2/heme oxygenase - 1 (Nrf-2/HO-1) activation (Sandireddy et al, 2016 ). In another study, Kwak et al ( 2017 ) revealed that baicalein, a flavonoid found in traditional Chinese herbal medicine can inhibit the oxidative-nitrosative stress and p38 MAPK activation and subsequently lead to alleviation of diabetic peripheral neuropathy.…”

Section: Role Of Antioxidants In the Prevention Of Age-related Diseasmentioning

confidence: 99%

Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases

et al. 2018

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Aging is the progressive loss of organ and tissue function over time. Growing older is positively linked to cognitive and biological degeneration such as physical frailty, psychological impairment, and cognitive decline. Oxidative stress is considered as an imbalance between pro- and antioxidant species, which results in molecular and cellular damage. Oxidative stress plays a crucial role in the development of age-related diseases. Emerging research evidence has suggested that antioxidant can control the autoxidation by interrupting the propagation of free radicals or by inhibiting the formation of free radicals and subsequently reduce oxidative stress, improve immune function, and increase healthy longevity. Indeed, oxidation damage is highly dependent on the inherited or acquired defects in enzymes involved in the redox-mediated signaling pathways. Therefore, the role of molecules with antioxidant activity that promote healthy aging and counteract oxidative stress is worth to discuss further. Of particular interest in this article, we highlighted the molecular mechanisms of antioxidants involved in the prevention of age-related diseases. Taken together, a better understanding of the role of antioxidants involved in redox modulation of inflammation would provide a useful approach for potential interventions, and subsequently promoting healthy longevity.

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Section: Role Of Antioxidants In the Prevention Of Age-related Diseasmentioning

confidence: 99%

Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases

et al. 2018

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“…Though ERK is classically known as an important regulator of cell proliferation, differentiation, and survival (51,52), its role in islet β-cell survival and function still remains controversial. Nonetheless, our previous studies (17,47), as well as other reports (53,54) suggest that the activation of the ERK pathway has a pro-survival role at least for islet β-cells in resisting gluco-or lipo-toxicity. As for the transcriptional regulation of the ERK pathway on PDX1, it is still unclear whether PDX1 is a direct downstream target gene of the ERK pathway or not.…”

Section: Discussionmentioning

confidence: 68%

“…For example, loss of PDX1 results in decreased expression of sarco/endoplasmic reticulum Ca(2+) pumps (SERCA2b), and in turn, leads to a reduction in ER Ca 2+ concentration and subsequent induction of ER stress (59). Besides, previous studies have suggested that ERK activation is involved in apelin, caveolin-1 deficiency or baicalein mediated alleviation of diabetesassociated ER stress and protection of pancreatic βcell against apoptosis (53,54,60). Based on these reports, we believe that TG partially elicits its protective effect on islet β-cells by preventing diabetes-related ER stress, which is also associated with ERK activation and subsequent improvement of PDX1 expression.…”

Section: Discussionmentioning

confidence: 99%

Tectorigenin enhances PDX1 expression and protects pancreatic β-cells by activating ERK and reducing ER stress

Yao

Chen

et al. 2020

Journal of Biological Chemistry

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Pancreas/duodenum homeobox protein 1 (PDX1) is an important transcription factor that regulates islet β-cell proliferation, differentiation, and function. Reduced expression of PDX1 is thought to contribute to β-cell loss and dysfunction in diabetes. Thus, promoting PDX1 expression can be an effective strategy to preserve β-cell mass and function. Previously, we established a PDX1 promoter-dependent luciferase system to screen agents that can promote PDX1 expression. Natural compound tectorigenin (TG) was identified as a promising candidate that could enhance the activity of the promoter for PDX1 gene. In this study, we first demonstrated that TG could promote the expression of PDX1 in β-cells via activating extracellular signal-related kinase (ERK), as indicated by increased phosphorylation of ERK; this effect was observed under either normal or glucotoxic/lipotoxic conditions. We then found that TG could suppress induced apoptosis and improved the viability of β-cells under glucotoxicity and lipotoxicity by activation of ERK and reduction of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress. These effects held true in vivo as well: prophylactic or therapeutic use of TG could obviously inhibit ER stress and decrease islet β-cell apoptosis in the pancreas of mice given a high-fat/high-sucrose diet (HFHSD), thus dramatically maintaining or restoring β-cell mass and islet size respectively. Accordingly, both prophylactic and therapeutic use of TG improved HFHSD impaired glucose metabolism in mice, as evidenced by ameliorating hyperglycemia and glucose intolerance. Taken together, TG, as an agent promoting PDX1 expression exhibits strong protective effects on islet β-cells both in vitro and in vivo.

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“…Exposure to TM and TG are known to induce ER stress. To examine the similarity between glucolipotoxicity and other ER stress inducers, the mRNA and protein levels of ER stress markers, Bip/GRP78 and CHOP were analyzed [ 9 ]. After exposed to TM, TG, and HG plus PA, Bip/GRP78 mRNA levels were significantly increased by 4.92 folds, 6.96 folds and 6.14 folds respectively ( Fig 6A , P <0.01).…”

Section: Resultsmentioning

confidence: 99%

Changes of MODY signal pathway genes in the endoplasmic reticulum stress in INS-1-3 cells

Dong

Zhao

et al. 2018

PLoS ONE

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ObjectiveMetabolic disturbances induce endoplasmic reticulum stress (ERS) in pancreatic beta cells. This study aims to investigate whether a common pathway exists in the ERS induced by various chemicals, including high levels of glucose and palmitate in INS-1-3 cells.MethodERS in INS-1-3 cells was induced by exposure cells to thapsigargin (TG), tunicamycin (TM) or palmitic acid (PA) +high glucose (HG). Digital gene expression (DGE) profiling technique was used to detect differentially expressed genes. The profile of gene expression was detected by gene oncology (GO) function and pathway enrichment analysis. Nkx6.1 over-expression was established in INS-1-3 cell lines by lentivirus infection to revert the inhibition of Nkx6.1 expression found in the situation of ERS. Real time reverse transcription polymerase chain reaction (RT-PCR) was used to verify the expression changes of key genes. Cell viability was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The apoptosis was determined by flow cytometry. INS-1-3 cell function was measured by glucose stimulated insulin secretion test(GSIS).ResultsAs compared to control, DGE demonstrated that there were 135, 57 and 74 differentially expressed genes in TM, TG and HG+PA groups, respectively. Those differentially expressed genes were enriched to ERS, antigen processing and presentation, protein export pathways, and interestingly, the maturity onset diabetes of the young (MODY) pathway. Nkx6.1 is one of common down-regulated gene in MODY signaling pathway among TM, TG and HG+PA groups. Over-expression of Nkx6.1 ameliorated glucolipotoxicity induced apoptosis rate by 45.4%, and increased proliferation by 40.9%. At the same time, GSIS increased by 1.82 folds.ConclusionsMODY pathway genes expression was changed in the state of ERS. Over-expression of Nkx6.1 protected the INS-1-3 cells from glucolipotoxicity.

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Baicalein protects rat insulinoma INS-1 cells from palmitate-induced lipotoxicity by inducing HO-1

Cited by 29 publications

References 39 publications

Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases

Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases

Tectorigenin enhances PDX1 expression and protects pancreatic β-cells by activating ERK and reducing ER stress

Changes of MODY signal pathway genes in the endoplasmic reticulum stress in INS-1-3 cells

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