Impact of HMG-CoA reductase inhibition on oxidant-induced injury in human retinal pigment epithelium cells

Jinqiao Qian, Kyle T. Keyes, Bo Long, Guanglin Chen, Yumei Ye

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

In addition to cholesterol-lowering effect, HMG-CoA reductase inhibition by statins has been shown to have protective effect in many cells type. The loss of vision in retinal degeneration disease associates with oxidative stress and apoptosis in retinal pigment epithelium (RPE) cell. This study was designed to examine the effect of statins on oxidant-induced damage in human RPE cells. Cultured human ARPE-19 (ARPE) cells were challenged with hydrogen peroxide (H 2O 2) plus tumor necrosis factor alpha (TNFα) in the presence or absence of statins or various stress signaling inhibitors, including anti-oxidants N-acetyl cysteine (NAC), the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium (DPI), and the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580. Apoptosis was evaluated by TUNEL analysis and cell viability was determined by MTT assay. Reactive oxygen species (ROS) were detected by 2′,7′- dichlorodihydrofluorescein diacetate (H 2DCFH-DA). Expression of p-p38 MAPK protein was measured by Western blot analysis. Our findings indicate that statins treatment significantly suppressed oxidant-induced ROS accumulation and RPE apoptosis. Statins increased cell viability in a dose-dependent manner. In addition, statins treatment prevented the activation of NADPH oxidase and p38 MAPK signaling induced by oxidative stress. These results suggest that statins protects ARPE cells from oxidative stress via an NADPH oxidase and/or p38 MAPK-dependent mechanisms, which may contribute to statins-induced beneficial effects on RPE function.

Original languageEnglish (US)
Pages (from-to)2480-2489
Number of pages10
JournalJournal of Cellular Biochemistry
Volume112
Issue number9
DOIs
StatePublished - Sep 2011

Fingerprint

Hydroxymethylglutaryl CoA Reductases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Retinal Pigments
Retinal Pigment Epithelium
Oxidants
Wounds and Injuries
p38 Mitogen-Activated Protein Kinases
Oxidative stress
NADP
Oxidoreductases
Oxidative Stress
Apoptosis
Reactive Oxygen Species
Cell Survival
Acetylcysteine
Cells
Retinal Diseases
Retinal Degeneration
Inhibition (Psychology)
In Situ Nick-End Labeling

Keywords

  • Apoptosis
  • Oxidative stress
  • p38
  • ROS
  • RPE

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Impact of HMG-CoA reductase inhibition on oxidant-induced injury in human retinal pigment epithelium cells. / Qian, Jinqiao; Keyes, Kyle T.; Long, Bo; Chen, Guanglin; Ye, Yumei.

In: Journal of Cellular Biochemistry, Vol. 112, No. 9, 09.2011, p. 2480-2489.

Research output: Contribution to journalArticle

Qian, Jinqiao ; Keyes, Kyle T. ; Long, Bo ; Chen, Guanglin ; Ye, Yumei. / Impact of HMG-CoA reductase inhibition on oxidant-induced injury in human retinal pigment epithelium cells. In: Journal of Cellular Biochemistry. 2011 ; Vol. 112, No. 9. pp. 2480-2489.
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