Idebenone Prevents Human Optic Nerve Head Astrocytes From Oxidative Stress, Apoptosis, and Senescence by Stabilizing BAX/Bcl-2 Ratio

Abstract

Purpose: Oxidative stress plays an important role in the pathogenesis of several neurodegenerative diseases including glaucoma. Astrocytes are supposed to play a role in glaucoma pathogenesis. This study investigates the antiapoptotic and cytoprotective effects of idebenone on optic nerve head astrocytes (ONHA) under oxidative stress.Methods: ONHA were treated with 1 to 150 mM idebenone. Cell viability (MTT assay and live-dead assay), induction of intracellular reactive oxygen species, senescence-associated b-galactosidase activity were investigated. In addition, apoptosis (detection of histone-associated DNA fragmentation), and expression of BAX and Bcl-2, and their mRNA were determined after 48 hours and after hydrogen peroxide (H 2 O 2 ) treatment.Results: Idebenone concentrations from 1 to 50 mM showed no effects on ONHA viability. Pretreatment with 10 mM idebenone led to an increase in viability of ONHA after H 2 O 2 treatment. In addition, idebenone pretreatment significantly attenuated the increase of histone-associated DNA fragmentation, induction of senescence-associated b-galactosidase, and intracellular reactive oxygen species after treatment with H 2 O 2 . When ONHA cells were treated with idebenone and H 2 O 2 , real-time polymerase chain reaction and Western blot analysis yielded an increased expression of Bcl-2 and a decrease of BAX compared with those cells that were treated with H 2 O 2 only.Conclusions: Idebenone reduced senescence, oxidative stress, and apoptotic cell death in cultured ONHA in vitro. Our results suggest that idebenone may help to protect ONHA in vivo, and therefore might be helpful in preventing the progression of glaucomatous degeneration.

Protein carbonylation after traumatic brain injury: cell specificity, regional susceptibility, and gender differences

“…Whereas astrocytes have the capacity to combat oxidative stress to the benefit of other adjacent cells, they themselves are still vulnerable to the actions of ROS, which can cause mitochondrial damage, accelerated senescence, and cell death [28,29]. Our results support these conclusions by demonstrating that at the site of lesion, astrocytes are the dominant cell type showing increased protein carbonylation post-CCI.…”

Idebenone Prevents Oxidative Stress, Cell Death and Senescence of Retinal Pigment Epithelium Cells by Stabilizing BAX/Bcl-2 Ratio

“…fibroblasts and keratinocytes [25,44]. Also, in the eye, SA-β-Gal is elevated in senescent cells [19]. So, the results of this study underline the pivotal role of oxidative stress in aging and apoptosis of RPE cells.…”

“…A previous study showed stronger effects with pre- than with posttreatment [18]. Also, we [19] and others [20,21,22] showed promising results with pretreatment; therefore, we chose this regimen again for the present study.…”

“…Previous studies demonstrated antiapoptotic effects of idebenone on several cell types [19,47,48,49]. To date, the use of idebenone and research regarding idebenone are focused on its protective effects on neuronal cells and tissues.…”

“…The first studies evaluated effects on the murine brain under hypoxia [50]; later on, it became a clinical treatment for patients with Friedreich's ataxia [10] and Leber's hereditary optic neuropathy [12]. Our recently published study showed its antiapoptotic, antioxidative, and antiaging effects on primary optic nerve head astrocytes in terms of glaucoma treatment [19]. Rather few studies evaluated other tissues, such as kidney, and also showed promising antioxidative effects [51].…”