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30, No. 2, 2012
Issue release date: July 2012
Section title: Original Paper
Cell Physiol Biochem 2012;30:439-449
(DOI:10.1159/000339037)

NADPH Oxidase 2-derived Reactive Oxygen Species are Involved in Dysfunction and Apoptosis of Pancreatic β-cells Induced by Low Density Lipoprotein

Li M.1 · Dou L.1,2 · Jiao J.1,2,3 · Lu Y.1,2 · Guo H.-B.1 · Man Y.1 · Wang S.1 · Li J.1,2 · These authors contributed equally to this work
1The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing;2Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing;3Department of Central Laboratory, General Hospital of Beijing Military Command, Beijing
email Corresponding Author

Abstract

Background: Increased levels of plasma cholesterol are a common feature of patient of type 2 diabetes. However, the links between elevated levels of low-density lipoprotein (LDL) and dysfunction of β-cells are still unclear. Methods: The apoE-/-mice were fed with a high-fat, cholesterol-rich diet for 8 weeks. Blood samples were collected from the mice for measurement of plasma glucose, lipids. The pancreas were embedded in OCT compound and frozen immediately in liquid nitrogen for further analysis. To examine the effects of LDL on β-cell function, insulin content, cell apoptosis and ROS production were measured in pancreatic islets of apoE-/-mice and mouse pancreatic β–cell line NIT-1. Relative cell signal pathways were determined by Western blot. Results: Decreased insulin content and increased apoptosis and ROS production were found in pancreatic islets of apoE-/-mice, accompanied by elevated plasma LDL. The ROS levels were significantly enhanced in NIT-1 cells exposed to LDL. Reduced insulin synthesis and glucose-stimulated insulin secretion and elevated apoptosis were reversed by suppression of NOX2 expression. Moreover, LDL induced dysfunction and apoptosis of pancreatic NIT-1 cells through JNK and p53 pathways, which were rescued by siRNA-mediated NOX2 reduction. Conclusions: NOX2-derived ROS may play a key role in LDL-induced dysfunction and apoptosis of pancreatic β-cells through JNK and p53 pathways.

© 2012 S. Karger AG, Basel


  

Key Words

  • LDL
  • NIT-1 cells
  • NADPH oxidase 2
  • Reactive oxygen species

  

Author Contacts

Shu Wang and Jian Li, Beijing Institute of Geriatrics, Beijing Hospital, Ministry of Health No.1, Dahua Road, Dong Dan, Beijing 100730 (China) Tel.+8610-58115048(o), Fax +86 10 65237929 E-Mail lijian@bjhmoh.cn (J. Li), ws3704@yahoo.com.cn (S.Wang)

  

Article Information

Accepted: June 15, 2012
Published online: July 06, 2012
Number of Print Pages : 11

  

Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry and Pharmacology)

Vol. 30, No. 2, Year 2012 (Cover Date: July 2012)

Journal Editor: Guggino W. (Baltimore, Md.), Lang F. (Tübingen)
ISSN: 1015-8987 (Print), eISSN: 1421-9778 (Online)

For additional information: http://www.karger.com/CPB


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background: Increased levels of plasma cholesterol are a common feature of patient of type 2 diabetes. However, the links between elevated levels of low-density lipoprotein (LDL) and dysfunction of β-cells are still unclear. Methods: The apoE-/-mice were fed with a high-fat, cholesterol-rich diet for 8 weeks. Blood samples were collected from the mice for measurement of plasma glucose, lipids. The pancreas were embedded in OCT compound and frozen immediately in liquid nitrogen for further analysis. To examine the effects of LDL on β-cell function, insulin content, cell apoptosis and ROS production were measured in pancreatic islets of apoE-/-mice and mouse pancreatic β–cell line NIT-1. Relative cell signal pathways were determined by Western blot. Results: Decreased insulin content and increased apoptosis and ROS production were found in pancreatic islets of apoE-/-mice, accompanied by elevated plasma LDL. The ROS levels were significantly enhanced in NIT-1 cells exposed to LDL. Reduced insulin synthesis and glucose-stimulated insulin secretion and elevated apoptosis were reversed by suppression of NOX2 expression. Moreover, LDL induced dysfunction and apoptosis of pancreatic NIT-1 cells through JNK and p53 pathways, which were rescued by siRNA-mediated NOX2 reduction. Conclusions: NOX2-derived ROS may play a key role in LDL-induced dysfunction and apoptosis of pancreatic β-cells through JNK and p53 pathways.

© 2012 S. Karger AG, Basel


  

Author Contacts

Shu Wang and Jian Li, Beijing Institute of Geriatrics, Beijing Hospital, Ministry of Health No.1, Dahua Road, Dong Dan, Beijing 100730 (China) Tel.+8610-58115048(o), Fax +86 10 65237929 E-Mail lijian@bjhmoh.cn (J. Li), ws3704@yahoo.com.cn (S.Wang)

  

Article Information

Accepted: June 15, 2012
Published online: July 06, 2012
Number of Print Pages : 11

  

Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry and Pharmacology)

Vol. 30, No. 2, Year 2012 (Cover Date: July 2012)

Journal Editor: Guggino W. (Baltimore, Md.), Lang F. (Tübingen)
ISSN: 1015-8987 (Print), eISSN: 1421-9778 (Online)

For additional information: http://www.karger.com/CPB


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Accepted: 6/15/2012
Published online: 7/6/2012
Issue release date: July 2012

Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

For additional information: http://www.karger.com/CPB


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.