Histone acetylation of glucose-induced thioredoxin-interacting protein gene expression in pancreatic islets

Bompada, Pradeep; Atac, David; Luan, Cheng; Andersson, Robin; Omella, Judit Domènech; Laakso, Emilia Ottosson; Wright, Jason; Groop, Leif; Marinis, Yang De

doi:10.1016/j.biocel.2016.10.022

Cited by 23 publications

(23 citation statements)

References 28 publications

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“…Indeed, TSA has been reported to induce Txnip gene expression in the INS-1 rat pancreatic beta cell line (Cha-Molstad et al 2009). A recent report has also shown that another HDACi, CI994, increased Txnip gene expression through activation of histone acetyl transferase p300 in INS-1 cells (Bompada et al 2016). Another HDACi, SAHA, also increased Txnip levels, leading to increased ROS (Ungerstedt et al 2012).…”

Section: Discussionmentioning

confidence: 98%

High dose of histone deacetylase inhibitors affects insulin secretory mechanism of pancreatic beta cell line

Yamato

2018

Endocrine Regulations

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Our results showed that HDACis caused failure to suppress insulin secretion at low glucose concentrations and enhance insulin secretion at high glucose concentrations. In other words, when these HDACis are used clinically, high doses of HDACis may cause hypoglycemia in the fasting state and hyperglycemia in the fed state. When using HDACis, physicians should, therefore, be aware of the capacity of these drugs to modulate the insulin secretory capacity of pancreatic beta cells.

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Section: Discussionmentioning

confidence: 98%

High dose of histone deacetylase inhibitors affects insulin secretory mechanism of pancreatic beta cell line

Yamato

2018

Endocrine Regulations

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“…Whereas the study from Bompada et al 53 aimed to investigate the role of p300 knock-out under pathological conditions (i.e., glucotoxicity), we rather questioned the role of p300 knock-down or inhibition under physiological conditions. This may therefore explain the discrepancy between our results and the above-mentioned studies 52 , 53 . Nevertheless, consistent with the role of p300 in Txnip gene expression in beta-cells 52 , 53 , evaluation of Txnip expression under p300 knock-down or inhibition revealed that the basal levels of Txnip were diminished (Supplemental Fig.…”

Section: Discussionmentioning

confidence: 89%

“…Whereas p300 plays an important role in beta-cell survival and seems therefore controlling expression of genes crucial for such purpose, we cannot exclude that specific environments and interacting partners will target p300 to other genes in beta-cells. Indeed, it has been reported that glucose stimulates the recruitment of p300 to the promoter region of the Txnip gene in human islets 52 and that p300 knockout prevents the expression of this pro-apoptotic factor Txnip in beta-cells exposed to high glucose 53 . Whereas the study from Bompada et al 53 aimed to investigate the role of p300 knock-out under pathological conditions (i.e., glucotoxicity), we rather questioned the role of p300 knock-down or inhibition under physiological conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, it has been reported that glucose stimulates the recruitment of p300 to the promoter region of the Txnip gene in human islets 52 and that p300 knockout prevents the expression of this pro-apoptotic factor Txnip in beta-cells exposed to high glucose 53 . Whereas the study from Bompada et al 53 aimed to investigate the role of p300 knock-out under pathological conditions (i.e., glucotoxicity), we rather questioned the role of p300 knock-down or inhibition under physiological conditions. This may therefore explain the discrepancy between our results and the above-mentioned studies 52 , 53 .…”

Section: Discussionmentioning

confidence: 99%

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Proteasomal degradation of the histone acetyl transferase p300 contributes to beta-cell injury in a diabetes environment

et al. 2018

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In type 2 diabetes, amyloid oligomers, chronic hyperglycemia, lipotoxicity, and pro-inflammatory cytokines are detrimental to beta-cells, causing apoptosis and impaired insulin secretion. The histone acetyl transferase p300, involved in remodeling of chromatin structure by epigenetic mechanisms, is a key ubiquitous activator of the transcriptional machinery. In this study, we report that loss of p300 acetyl transferase activity and expression leads to beta-cell apoptosis, and most importantly, that stress situations known to be associated with diabetes alter p300 levels and functional integrity. We found that proteasomal degradation is the mechanism subserving p300 loss in beta-cells exposed to hyperglycemia or pro-inflammatory cytokines. We also report that melatonin, a hormone produced in the pineal gland and known to play key roles in beta-cell health, preserves p300 levels altered by these toxic conditions. Collectively, these data imply an important role for p300 in the pathophysiology of diabetes.

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“…Initially described as an adaptive immune system in bacteria, it has been extensively developed as an RNA-guided genome editing tool, allowing precise manipulation of specific genomic loci and facilitating detailed investigation of targeted gene functions or diseases. CRISPR-Cas9 technology has been used for genome editing in induced pluripotent stem cells [1, 2] primary human endothelial cells [3] and the INS-1 [4, 5] and MIN6 [6, 7] β-cell lines, among others.…”

Section: Introductionmentioning

confidence: 99%

Identifying Signalling Pathways Regulated by GPRC5B in β-Cells by CRISPR-Cas9-Mediated Genome Editing

Atanes¹,

Ruz‐Maldonado

Hawkes

et al. 2018

Cell Physiol Biochem

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Background/Aims: CRISPR-Cas9, a RNA-guided targeted genome editing tool, has revolutionized genetic engineering by offering the ability to precisely modify DNA. GPRC5B is an orphan receptor belonging to the group C family of G protein-coupled receptors (GPCRs). In this study, we analysed the functional roles of the Gprc5b receptor in MIN6 β-cells using CRISPR-Cas9 and transient over-expression of Gprc5b. Methods: The optimal transfection reagent for use in MIN6 β-cells was determined by analysing efficiency of GFP plasmid delivery by cell sorting. A MIN6 β-cell line in which Gprc5b expression was knocked down (Gprc5b KD) was generated using CRISPR-Cas9 technology. Gprc5b receptor mRNA expression, proliferation, apoptosis, Cignal 45-Pathway Reporter Array signalling and western blot assays were carried out using Gpcr5b KD MIN6 β-cells that had been transiently transfected with different concentrations of mouse Gprc5b plasmid to over-express Gprc5b. Results: JetPRIME® was the best candidate for MIN6 β-cell transfection, providing approximately 30% transfection efficiency. CRISPR-Cas9 technology targeting Gprc5b led to stable knock-down of this receptor in MIN6 β-cells and its re-expression induced proliferation and potentiated cytokine- and palmitate-induced apoptosis. The Cignal 45 Reporter analysis indicated Gprc5b-dependent regulation of apoptotic and proliferative pathways, and western blotting confirmed activation of signalling via TGF-β and IFNγ. Conclusion: This study provides evidence of CRISPR-Cas9 technology being used to down-regulate Gprc5b expression in MIN6 β-cells. This strategy allowed us to identify signalling pathways linking GPRC5B receptor expression to β-cell proliferation and apoptosis.

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Histone acetylation of glucose-induced thioredoxin-interacting protein gene expression in pancreatic islets

Cited by 23 publications

References 28 publications

High dose of histone deacetylase inhibitors affects insulin secretory mechanism of pancreatic beta cell line

High dose of histone deacetylase inhibitors affects insulin secretory mechanism of pancreatic beta cell line

Proteasomal degradation of the histone acetyl transferase p300 contributes to beta-cell injury in a diabetes environment

Identifying Signalling Pathways Regulated by GPRC5B in β-Cells by CRISPR-Cas9-Mediated Genome Editing

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