Apocynin decreases AGEs-induced stimulation of NF-κB protein expression in vascular smooth muscle cells from GK rats.

Abstract

CONTEXT:

Elevated oxidative stress plays a key role in diabetes-associated vascular disease. Excessive production of reactive oxygen species via advanced glycation end products (AGEs) activates peroxisome proliferator-activated receptor gamma (PPARγ) and the transcription factor nuclear factor-kB (NF-κB) in aortic vascular smooth muscle cells (VSMCs). Apocynin, a drug with an antioxidant effect, has also been proposed as a therapeutic agent for atherosclerotic disease.

OBJECTIVES:

This work investigates the effects of apocynin on the PPARγ and NF-κB protein expression evoked by AGEs in cultured VSMCs from Goto-Kakisaki (GK) rats, a non-obese insulin model of both insulin resistance and type 2 diabetes.

MATERIALS AND METHODS:

VSMCs, isolated from aortas of GK and non-diabetic rats, were cultured. The expression of proteins was evaluated by Western blot. The blood glucose concentration was measured with a blood glucose test meter. The diabetes of GK rats was controlled by blood glucose and insulin determinations (non-fasting values). The serum insulin concentration was determined by radioimmunoassay.

RESULTS:

In VSMCs from non-diabetic and GK rats, apocynin (1 and 10 µM) abolished the protein overexpression of NF-κB induced by glycated bovine serum albumin (AGEs-BSA) incubation. However, apocynin (1 and 10 µM) enhanced the expression of PPARγ protein in the presence of AGEs-BSA (100 μg/mL) in VSMCs from non-diabetic, but not from GK rats.

CONCLUSION:

These findings suggest that apocynin decreases the incidence of alterations in VSMCs induced by AGEs through the reduction of NF-κB and may represent an attractive therapeutic approach to treat diabetes mellitus.

• Authors: Cristina Oliveira Silva, Odair Alves da Silva, Gloria Pinto Duarte, Bernard Descomps, Saad Lahlou
• Journal: Pharmaceutical biology (Pharm Biol) Vol. 53 Issue 4 Pg. 488-93 (Apr 2015) ISSN: 1744-5116 [Electronic] England
• PMID: 25471209 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetophenones
• Antioxidants
• Glycation End Products, Advanced
• NF-kappa B
• PPAR gamma
• advanced glycation end products-bovine serum albumin
• Serum Albumin, Bovine
• acetovanillone

Topics

• Acetophenones (pharmacology)
• Animals
• Antioxidants (pharmacology)
• Aorta, Thoracic (cytology, drug effects, metabolism)
• Blotting, Western
• Cell Culture Techniques
• Cells, Cultured
• Electrophoresis, Polyacrylamide Gel
• Glycation End Products, Advanced (pharmacology)
• Male
• Muscle, Smooth, Vascular (cytology, drug effects, metabolism)
• Myocytes, Smooth Muscle (drug effects, metabolism)
• NF-kappa B (biosynthesis)
• PPAR gamma (biosynthesis)
• Rats, Inbred Strains
• Serum Albumin, Bovine (pharmacology)