Environmental level bisphenol A accelerates alterations of the reno-cardiac axis by the MAPK cascades in male diabetic rats: An analysis based on transcriptomic profiling and bioinformatics

Abstract Purpose: This study was designed to investigate the mechanism of Dapagliflozin (Dapa) cardioprotection against diabetic cardiomyopathy (DCM). Structural and functional changes in the heart as well as decrease of Erythropoietin (EPO) levels were reported in DCM. EPO simultaneously activates three pathways: the Janus-activated kinase–signal transducer and activator of transcription (JAK2/STAT5), phosphatidylinositol-3-kinase-Akt (PI3K/Akt), and extracellular signal-related kinase (ERK/MAPK) cascades, that result in proliferation and differentiation of cardiac cells.Methods and Results: DCM was induced by a high fat diet for 10 weeks followed by administration of streptozotocin. After confirmation of diabetes, rats were divided randomly to 5 groups: Group 1; normal control group, Group 2; untreated diabetic group and Groups (3-5); diabetic groups received Dapa daily (0.75 mg, 1.5 or 3 mg /Kg, p.o) respectively for a month. At the end of the experiment, full anaesthesia was induced in all rats using ether inhalation and ECG was recorded. Blood samples were collected then rats were sacrificed and their heart were dissected out and processed for biochemical and histopathological studies. Untreated diabetic rats showed abnormal ECG pattern, elevation of serum cardiac enzymes, decrease EPO levels, downregulation of P-Akt, P-JAK2 and pMAPK pathways, abnormal histological structure of the heart and increase immunostaining intensity of P53 and TNF α in the cardiomyocytes. Dapa in a dose dependent manner attenuated the alterations in the previously mentioned parameters. Conclusion: The cardioprotective effect of Dapa could be mediated by increasing EPO levels and activation of P-Akt, P-JAK2 and pMAPK signalling cascades which in turn decrease apoptosis.

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Bisphenol A exposure triggers apoptosis via three signaling pathways in Caenorhabditis elegans

RSC Advances ◽

10.1039/c7ra04512c ◽

2017 ◽

Vol 7 (52) ◽

pp. 32624-32631 ◽

Cited By ~ 1

Author(s):

Yun Wang ◽

Lianfeng Zhang ◽

Xun Luo ◽

Shunchang Wang ◽

Yuanyuan Wang

Keyword(s):

Dna Damage ◽

Caenorhabditis Elegans ◽

Growth Factor ◽

Bisphenol A ◽

Signaling Pathways ◽

Dna Damage Response ◽

Mitogen Activated Protein Kinase ◽

Mapk Cascades ◽

Damage Response ◽

Mitogen Activated Protein

Bisphenol A can trigger germline apoptosis via three signaling pathways including DNA damage response (DDR) pathway, mitogen-activated protein kinase (MAPK) cascades and insulin-like growth factor-1 (IGF-1) network in Caenorhabditis elegans.

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Transcriptomic profiling of bisphenol A (BPA)-treated human mammosphere-derived epithelial cells

Signaling Pathways Project Datasets ◽

10.1621/7yaeirdimq ◽

2015 ◽

Author(s):

YI Weng

Keyword(s):

Epithelial Cells ◽

Bisphenol A ◽

Transcriptomic Profiling

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Sites of Insulin Action Using Ferritin Labeling

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066759 ◽

1971 ◽

Vol 29 ◽

pp. 540-541

Author(s):

Burton B. Silver ◽

Ronald S. Nelson

Keyword(s):

Electron Microscopy ◽

Binding Sites ◽

Anterior Pituitary ◽

Insulin Action ◽

Diabetic Rats ◽

Insulin Antibody ◽

Fat Pad ◽

Target Organs ◽

Uranium Salts ◽

Sugar Levels

Some investigators feel that insulin does not enter cells but exerts its influence in some manner on the cell surface. Ferritin labeling of insulin and insulin antibody was used to determine if binding sites of insulin to specific target organs could be seen with electron microscopy.Alloxanized rats were considered diabetic if blood sugar levels were in excess of 300 mg %. Test reagents included ferritin, ferritin labeled insulin, and ferritin labeled insulin antibody. Target organs examined were were diaphragm, kidney, gastrocnemius, fat pad, liver and anterior pituitary. Reagents were administered through the left common carotid. Survival time was at least one hour in test animals. Tissue incubation studies were also done in normal as well as diabetic rats. Specimens were fixed in gluteraldehyde and osmium followed by staining with lead and uranium salts. Some tissues were not stained.

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Probing the Chemistry and Spectroscopy of Radiation-Sensitive Polymers by Parallel-Detection EELS

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010013376x ◽

1990 ◽

Vol 48 (2) ◽

pp. 34-35

Author(s):

E. G. Rightor ◽

G. P. Young

Keyword(s):

Electron Beam ◽

Bisphenol A ◽

Energy Loss ◽

Parallel Detection ◽

Commercial Grade ◽

Incident Electron Beam ◽

Ptfe Sample ◽

Spectroscopic Information ◽

Edge Features ◽

Electron Energy Loss

Investigation of neat polymers by TEM is often thwarted by their sensitivity to the incident electron beam, which also limits the usefulness of chemical and spectroscopic information available by electron energy loss spectroscopy (EELS) for these materials. However, parallel-detection EELS systems allow reduced radiation damage, due to their far greater efficiency, thereby promoting their use to obtain this information for polymers. This is evident in qualitative identification of beam sensitive components in polymer blends and detailed investigations of near-edge features of homopolymers.Spectra were obtained for a poly(bisphenol-A carbonate) (BPAC) blend containing poly(tetrafluoroethylene) (PTFE) using a parallel-EELS and a serial-EELS (Gatan 666, 607) for comparison. A series of homopolymers was also examined using parallel-EELS on a JEOL 2000FX TEM employing a LaB6 filament at 100 kV. Pure homopolymers were obtained from Scientific Polymer Products. The PTFE sample was commercial grade. Polymers were microtomed on a Reichert-Jung Ultracut E and placed on holey carbon grids.

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