RGD Reference Report - PKC-delta-dependent activation of oxidative stress in adipocytes of obese and insulin-resistant mice: role for NADPH oxidase. - Rat Genome Database

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PKC-delta-dependent activation of oxidative stress in adipocytes of obese and insulin-resistant mice: role for NADPH oxidase.

Authors: Talior, I  Tennenbaum, T  Kuroki, T  Eldar-Finkelman, H 
Citation: Talior I, etal., Am J Physiol Endocrinol Metab. 2005 Feb;288(2):E405-11. Epub 2004 Oct 26.
RGD ID: 1642527
Pubmed: PMID:15507533   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpendo.00378.2004   (Journal Full-text)

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 obese and insulin-resistant mice (HF). ROS production was also associated with the increased activity of 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, 1 mM), xanthine oxidase (allopurinol, 100 microM), AGE formation (aminoguanidine, 10 microM), or the mitochondrial uncoupler (FCCP, 10 microM) had no effect. Rottlerin, a selective PKC-delta inhibitor, suppressed ROS levels by approximately 50%. However, neither GO-6976 nor LY-333531, effective inhibitors toward conventional PKC or PKC-beta, respectively, 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 twofold 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, these results suggest that PKC-delta is responsible for elevated intracellular ROS production in HF adipocytes, and this is mediated by high glucose and NADPH oxidase.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Insulin Resistance  ISOPrkcd (Mus musculus)1642527; 1642527associated with Obesity and protein:increased activity:adipocyteRGD 
Insulin Resistance  IMP 1642527associated with Obesity and protein:increased activity:adipocyteRGD 

Objects Annotated

Genes (Rattus norvegicus)
Prkcd  (protein kinase C, delta)

Genes (Mus musculus)
Prkcd  (protein kinase C, delta)

Genes (Homo sapiens)
PRKCD  (protein kinase C delta)


Additional Information