Pancreatic β-Cell Death in Response to Pro-Inflammatory Cytokines Is Distinct from Genuine Apoptosis

Collier, J. Jason; Burke, Susan J.; Eisenhauer, Mary E.; Lu, Danhong; Sapp, Renee C.; Frydman, Carlie Joelle; Campagna, Shawn R.

doi:10.1371/journal.pone.0022485

Cited by 68 publications

(68 citation statements)

References 80 publications

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“…It indicated that these metabolic changes are major mediators of oncogenic stress in Bcr-Abl cells. In a report done by Collier et al (2011), using 832/13 and INS-1E rat insulinoma cells, the apoptosis is unlikely to be the primary pathway underlying b-cell death in response to IL-1b + c-IFN (Collier et al, 2011). Results demonstrate that pancreatic b-cells undergo apoptosis in response to camptothecin or staurosporine, but not pro-inflammatory cytokines.…”

Section: Cancer Cellsmentioning

confidence: 82%

Cell Metabolomics

Zhang

Sun²,

Xu³

et al. 2013

OMICS: A Journal of Integrative Biology

164

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Metabolomics technologies enable the examination and identification of endogenous biochemical reaction products, revealing information on the precise metabolic pathways and processes within a living cell. Metabolism is either directly or indirectly involved with every aspect of cell function, and metabolomics is thus believed to be a reflection of the phenotype of any cell. Metabolomics analysis of cells has many potential applications and advantages compared to currently used methods in the postgenomics era. Cell metabolomics is an emerging field that addresses fundamental biological questions and allows one to observe metabolic phenomena in cells. Cell metabolomics consists of four sequential steps: (a) sample preparation and extraction, (b) metabolic profiles of low-weight metabolites based on MS or NMR spectroscopy techniques, (c) pattern recognition approaches and bioinformatics data analysis, (d) metabolites identification resulting in putative biomarkers and molecular targets. The biomarkers are eventually placed in metabolic networks to provide insight on the cellular biochemical phenomena. This article analyzes the recent developments in use of metabolomics to characterize and interpret the cellular metabolome in a wide range of pathophysiological and clinical contexts, and the putative roles of the endogenous small molecule metabolites in this new frontier of postgenomics biology and systems medicine.

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Section: Cancer Cellsmentioning

confidence: 82%

Cell Metabolomics

Zhang

Sun²,

Xu³

et al. 2013

OMICS: A Journal of Integrative Biology

164

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“…Cell lysis, luciferase assays, and normalization to total protein content were carried out as described previously (27). CCL2 and CCL20 secreted into the media were detected using rat Quantikine (CCL2) or DuoSet (CCL20) ELISA kits from R&D Systems, Inc. (Minneapolis, MN) according to the manufacturer's suggested protocol.…”

Section: Methodsmentioning

confidence: 99%

Thiobenzothiazole-modified Hydrocortisones Display Anti-inflammatory Activity with Reduced Impact on Islet β-Cell Function

Burke

May

Noland³

et al. 2015

Journal of Biological Chemistry

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Background: Glucocorticoids impair islet ␤-cell function via glucocorticoid receptor (GR) activation. Results: Thiobenzothiazole-modified hydrocortisone compounds exhibit anti-inflammatory properties with reduced impact on insulin secretion. Conclusion: Novel glucocorticoids can be engineered to reduce impact on ␤-cell mass and function. Significance: Improved GR agonists will be beneficial in a variety of clinical settings.

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“…Cellular lysates were harvested using the M-PER Mammalian Protein Extraction Reagent (Thermo Scientific) supplemented with a cocktail of protease and phosphatase inhibitors (Thermo Scientific). Proteins were quantified using a BCA assay (Thermo Scientific), and immunoblotting was performed as previously described (11). Antibodies used for detection of proteins were from the following manufacturers: Santa Cruz Biotechnologies (PO 4-IB␣ and IB␣), Cell Signaling (PO4-Y701 STAT1), and Sigma-Aldrich (␤-actin).…”

mentioning

confidence: 99%

NF-κB and STAT1 control CXCL1 and CXCL2 gene transcription

Burke

Sparer

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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135

119

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Diabetes mellitus results from immune cell invasion into pancreatic islets of Langerhans, eventually leading to selective destruction of the insulin-producing ␤-cells. How this process is initiated is not well understood. In this study, we investigated the regulation of the CXCL1 and CXCL2 genes, which encode proteins that promote migration of CXCR2 ϩ cells, such as neutrophils, toward secreting tissue. Herein, we found that IL-1␤ markedly enhanced the expression of the CXCL1 and CXCL2 genes in rat islets and ␤-cell lines, which resulted in increased secretion of each of these proteins. CXCL1 and CXCL2 also stimulated the expression of specific integrin proteins on the surface of human neutrophils. Mutation of a consensus NF-B genomic sequence present in both gene promoters reduced the ability of IL-1␤ to promote transcription. In addition, IL-1␤ induced binding of the p65 and p50 subunits of NF-B to these consensus B regulatory elements as well as to additional B sites located near the core promoter regions of each gene. Additionally, serine-phosphorylated STAT1 bound to the promoters of the CXCL1 and CXCL2 genes. We further found that IL-1␤ induced specific posttranslational modifications to histone H3 in a time frame congruent with transcription factor binding and transcript accumulation. We conclude that IL-1␤-mediated regulation of the CXCL1 and CXCL2 genes in pancreatic ␤-cells requires stimulus-induced changes in histone chemical modifications, recruitment of the NF-B and STAT1 transcription factors to genomic regulatory sequences within the proximal gene promoters, and increases in phosphorylated forms of RNA polymerase II.

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Pancreatic β-Cell Death in Response to Pro-Inflammatory Cytokines Is Distinct from Genuine Apoptosis

Cited by 68 publications

References 80 publications

Cell Metabolomics

Cell Metabolomics

Thiobenzothiazole-modified Hydrocortisones Display Anti-inflammatory Activity with Reduced Impact on Islet β-Cell Function

NF-κB and STAT1 control CXCL1 and CXCL2 gene transcription

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