Probucol decreases homocysteine-stimulated CRP production in rat aortic smooth muscle cells via regulating HO-1/NADPH oxidase/ROS/p38 pathway.

Abstract

The elevated homocysteine level is an independent risk factor for atherosclerosis, which is characterized as a chronic inflammatory disease associated with oxidative stress. We have confirmed that homocysteine can stimulate the production of C-reactive protein (CRP) in rat aortic smooth muscle cells (RASMCs). In the present study, we investigated the role of probucol in homocysteine-induced CRP expression in cultured RASMCs and high-methionine-diet-induced hyperhomocysteinemic rats. The results showed that probucol decreased homocysteine-induced CRP mRNA and protein expression in RASMCs in a concentration-dependent manner. In addition, the animal experiment showed that probucol not only inhibited CRP expression in the vessel wall but also reduced the circulating CRP level in hyperhomocysteinemic rats. Further investigations revealed that probucol markedly increased heme oxygenase-1 activity, suppressed nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, diminished superoxide anion generation, and decreased p38 phosphorylation in RASMCs and hyperhomocysteinemic rat aorta. These data demonstrate that probucol can inhibit homocysteine-induced CRP generation by interfering with the NADPH oxidase/p38 signal pathway in RASMCs, which will provide new evidence for the anti-inflammatory and anti-atherosclerotic effects of probucol.

• Authors: Yuxia Li, Qun Zhao, Yuan Cao, Jigang Si, Jing Li, Kai Cao, Xiaoming Pang
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 53 Issue 2 Pg. 212-219 (Feb 04 2021) ISSN: 1745-7270 [Electronic] China
• PMID: 33382068 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Reactive Oxygen Species
• Homocysteine
• C-Reactive Protein
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat
• NADPH Oxidases
• p38 Mitogen-Activated Protein Kinases
• Probucol

Topics

• Animals
• Aorta (metabolism)
• C-Reactive Protein (biosynthesis)
• Heme Oxygenase (Decyclizing) (metabolism)
• Homocysteine (pharmacology)
• MAP Kinase Signaling System (drug effects)
• Muscle, Smooth, Vascular (metabolism)
• Myocytes, Smooth Muscle (metabolism)
• NADPH Oxidases (metabolism)
• Probucol (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)