AJP - Endo Watch the video to learn how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab (October 26, 2004). doi:10.1152/ajpendo.00378.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
288/2/E405    most recent
00378.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Talior, I.
Right arrow Articles by Eldar-Finkelman, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Talior, I.
Right arrow Articles by Eldar-Finkelman, H.
Submitted on August 16, 2004
Accepted on October 21, 2004

Protein Kinase C-{delta} Dependent Activation of Oxidative Stress In Adipocytes of Obese and Insulin Resistant Mice: Role for NADPH oxidase

Ilana Talior1, Tamar Tennenbaum2, Toshio Kuroki3, and Hagit Eldar-Finkelman1*

1 Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
2 Faculty of Life Science, Bar-Ilan University, Ramat-Gan, Israel
3 Institute Molecular Oncology, Showa University, Tokyo, Japan

* To whom correspondence should be addressed. E-mail: heldar{at}post.tau.ac.il.

Oxidative stress is thought to be one of the causative factors contributing to insulin resistance and type 2 diabetes. Previously, we showed that reactive oxygen species (ROS) production is significantly increased in adipocytes from high-fat diet-induced obesity and insulin-resistant mice (HF). ROS production was also associated with the increased activity of protein kinase C-{delta} (PKC-{delta}). In the present studies, we hypothesized that PKC-{delta} contributes to ROS generation and determined their intracellular source. NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI) reduced ROS levels by 50% in HF adipocytes, and inhibitors of NO synthase (L-NAME, 1mM), Xanthine oxidase (allopurinol, 100µM), AGE formation (aminoguanidine, 10µM), or the mitochondrial uncoupler (FCCP, 10µM) had no effect. Rottlerin a selective PKC-{delta} inhibitor, suppressed ROS levels by approximately 50%. However, neither GO6976 nor LY333531, effective inhibitors toward conventional PKC or PKC-{beta}, respectively, did not significantly altered ROS levels in HF adipocytes. Subsequently, adenoviral-mediated expression of wild-type PKC-{delta}, or its dominant negative mutant (DN-PKC-{delta}) in HF adipocytes resulted in either a two-fold increase in ROS levels, or their suppression by 20%, respectively. In addition, both ROS levels and PKC-{delta} activity were sharply reduced by glucose depletion. Taken together, we suggest that PKC-{delta} is responsible for elevated intracellular ROS production in HF adipocytes, and this is mediated by high glucose and NADPH oxidase.




This article has been cited by other articles:


Home page
 Mol. Cell. Biol.Home page
S. Sudarshan, C. Sourbier, H.-S. Kong, K. Block, V. A. V. Romero, Y. Yang, C. Galindo, M. Mollapour, B. Scroggins, N. Goode, et al.
Fumarate Hydratase Deficiency in Renal Cancer Induces Glycolytic Addiction and Hypoxia-Inducible Transcription Factor 1{alpha} Stabilization by Glucose-Dependent Generation of Reactive Oxygen Species
Mol. Cell. Biol., August 1, 2009; 29(15): 4080 - 4090.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H.-W. Koon, Y. S. Kim, H. Xu, A. Kumar, D. Zhao, I. Karagiannides, P. R. Dobner, and C. Pothoulakis
Neurotensin induces IL-6 secretion in mouse preadipocytes and adipose tissues during 2,4,6,-trinitrobenzensulphonic acid-induced colitis
PNAS, May 26, 2009; 106(21): 8766 - 8771.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
N. Bashan, J. Kovsan, I. Kachko, H. Ovadia, and A. Rudich
Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species
Physiol Rev, January 1, 2009; 89(1): 27 - 71.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
Z. Liberman, B. Plotkin, T. Tennenbaum, and H. Eldar-Finkelman
Coordinated phosphorylation of insulin receptor substrate-1 by glycogen synthase kinase-3 and protein kinase C{beta}II in the diabetic fat tissue
Am J Physiol Endocrinol Metab, June 1, 2008; 294(6): E1169 - E1177.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
W.-S. Wu, R. K. Tsai, C. H. Chang, S. Wang, J.-R. Wu, and Y.-X. Chang
Reactive Oxygen Species Mediated Sustained Activation of Protein Kinase C {alpha} and Extracellular Signal-Regulated Kinase for Migration of Human Hepatoma Cell Hepg2
Mol. Cancer Res., October 1, 2006; 4(10): 747 - 758.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
M. B. Marrero, A. K. Banes-Berceli, D. M. Stern, and D. C. Eaton
Role of the JAK/STAT signaling pathway in diabetic nephropathy
Am J Physiol Renal Physiol, April 1, 2006; 290(4): F762 - F768.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.