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Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass and improves bioenergetic function in optic nerve head astrocytes.

Noh YH, Kim KY, Shim MS, Choi SH, Choi S, Ellisman MH, Weinreb RN, Perkins GA, Ju WK - Cell Death Dis (2013)

Bottom Line: In contrast, CoQ10 not only prevented activation of ONH astrocytes but also significantly decreased SOD2 and HO-1 protein expression in the ONH astrocytes against oxidative stress.Finally, oxidative stress triggered the upregulation of OXPHOS Cx protein expression, as well as reduction of cellular adeonsine triphosphate (ATP) production and increase of ROS generation in the ONH astocytes.However, CoQ10 preserved OXPHOS protein expression and cellular ATP production, as well as decreased ROS generation in the ONH astrocytes.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Optic Nerve Biology, Hamilton Glaucoma Center and Department of Ophthalmology, University of California, San Diego, La Jolla, CA, USA.

ABSTRACT
Oxidative stress contributes to dysfunction of glial cells in the optic nerve head (ONH). However, the biological basis of the precise functional role of mitochondria in this dysfunction is not fully understood. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain and a potent antioxidant, acts by scavenging reactive oxygen species (ROS) for protecting neuronal cells against oxidative stress in many neurodegenerative diseases. Here, we tested whether hydrogen peroxide (100 μM H2O2)-induced oxidative stress alters the mitochondrial network, oxidative phosphorylation (OXPHOS) complex (Cx) expression and bioenergetics, as well as whether CoQ10 can ameliorate oxidative stress-mediated alterations in mitochondria of the ONH astrocytes in vitro. Oxidative stress triggered the activation of ONH astrocytes and the upregulation of superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) protein expression in the ONH astrocytes. In contrast, CoQ10 not only prevented activation of ONH astrocytes but also significantly decreased SOD2 and HO-1 protein expression in the ONH astrocytes against oxidative stress. Further, CoQ10 prevented a significant loss of mitochondrial mass by increasing mitochondrial number and volume density and by preserving mitochondrial cristae structure, as well as promoted mitofilin and peroxisome-proliferator-activated receptor-γ coactivator-1 protein expression in the ONH astrocyte, suggesting an induction of mitochondrial biogenesis. Finally, oxidative stress triggered the upregulation of OXPHOS Cx protein expression, as well as reduction of cellular adeonsine triphosphate (ATP) production and increase of ROS generation in the ONH astocytes. However, CoQ10 preserved OXPHOS protein expression and cellular ATP production, as well as decreased ROS generation in the ONH astrocytes. On the basis of these observations, we suggest that oxidative stress-mediated mitochondrial dysfunction or alteration may be an important pathophysiological mechanism in the dysfunction of ONH astrocytes. CoQ10 may provide new therapeutic potentials and strategies for protecting ONH astrocytes against oxidative stress-mediated mitochondrial dysfunction or alteration in glaucoma and other optic neuropathies.

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CoQ10 prevents the alteration of mitochondrial bioenergetics caused by oxidative stress. Pretreatment of CoQ10 significantly restored cell viability to 92.6±4.6% of the control level in the ONH astrocytes exposed to H2O2. In comparison with control ONH astrocytes, H2O2-induced oxidative stress significantly increased ROS generation in the ONH astrocytes. In contrast, pretreatment of CoQ10 significantly decreased ROS generation in the ONH astrocytes exposed to H2O2. In addition, H2O2-induced oxidative stress significantly decreased the cellular ATP level in the ONH astrocytes. However, pretreatment of CoQ10 significantly restored the cellular ATP level in the ONH astrocytes exposed to H2O2. Values are mean±S.D. *P<0.05 and **P<0.01 compared with vehicle-treated control ONH astrocytes or H2O2-treated ONH astrocytes. CoQ10, coenzyme Q10; H2O2, hydrogen peroxide
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fig7: CoQ10 prevents the alteration of mitochondrial bioenergetics caused by oxidative stress. Pretreatment of CoQ10 significantly restored cell viability to 92.6±4.6% of the control level in the ONH astrocytes exposed to H2O2. In comparison with control ONH astrocytes, H2O2-induced oxidative stress significantly increased ROS generation in the ONH astrocytes. In contrast, pretreatment of CoQ10 significantly decreased ROS generation in the ONH astrocytes exposed to H2O2. In addition, H2O2-induced oxidative stress significantly decreased the cellular ATP level in the ONH astrocytes. However, pretreatment of CoQ10 significantly restored the cellular ATP level in the ONH astrocytes exposed to H2O2. Values are mean±S.D. *P<0.05 and **P<0.01 compared with vehicle-treated control ONH astrocytes or H2O2-treated ONH astrocytes. CoQ10, coenzyme Q10; H2O2, hydrogen peroxide

Mentions: To determine whether H2O2-induced oxidative stress alters mitochondrial bioenergetics in ONH astrocytes and whether CoQ10 treatment inhibits the alteration of mitochondrial bioenergetics, we measured cell viability, ROS generation and cellular ATP level. As shown in Figure 7, our findings show that H2O2-induced oxidative stress significantly decreased cell viability to 80.8±5.4% of the control value in the ONH astrocytes (P<0.05). However, pretreatment of CoQ10 significantly boosted cell viability to 92.6±4.6% in the ONH astrocytes exposed to H2O2 (P=0.001). In comparison with control ONH astrocytes, H2O2-induced oxidative stress significantly increased ROS generation by 7.82±0.81-fold over the control in the ONH astrocytes (P=0.01). In contrast, pretreatment of CoQ10 significantly decreased ROS generation to 4.67±0.83-fold of the control in the ONH astrocytes exposed to H2O2 (P<0.05). In addition, we found that H2O2-induced oxidative stress significantly decreased the cellular ATP level to 83.8±3.7% of the control value in the ONH astrocytes (P<0.01). However, pretreatment of CoQ10 nearly completely restored the cellular ATP level (96.9±4.3% of the control) in the ONH astrocytes exposed to H2O2 (P<0.05), suggesting that CoQ10 restores bioenergetic function in the ONH astrocytes to counter oxidative stress.


Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass and improves bioenergetic function in optic nerve head astrocytes.

Noh YH, Kim KY, Shim MS, Choi SH, Choi S, Ellisman MH, Weinreb RN, Perkins GA, Ju WK - Cell Death Dis (2013)

CoQ10 prevents the alteration of mitochondrial bioenergetics caused by oxidative stress. Pretreatment of CoQ10 significantly restored cell viability to 92.6±4.6% of the control level in the ONH astrocytes exposed to H2O2. In comparison with control ONH astrocytes, H2O2-induced oxidative stress significantly increased ROS generation in the ONH astrocytes. In contrast, pretreatment of CoQ10 significantly decreased ROS generation in the ONH astrocytes exposed to H2O2. In addition, H2O2-induced oxidative stress significantly decreased the cellular ATP level in the ONH astrocytes. However, pretreatment of CoQ10 significantly restored the cellular ATP level in the ONH astrocytes exposed to H2O2. Values are mean±S.D. *P<0.05 and **P<0.01 compared with vehicle-treated control ONH astrocytes or H2O2-treated ONH astrocytes. CoQ10, coenzyme Q10; H2O2, hydrogen peroxide
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824651&req=5

fig7: CoQ10 prevents the alteration of mitochondrial bioenergetics caused by oxidative stress. Pretreatment of CoQ10 significantly restored cell viability to 92.6±4.6% of the control level in the ONH astrocytes exposed to H2O2. In comparison with control ONH astrocytes, H2O2-induced oxidative stress significantly increased ROS generation in the ONH astrocytes. In contrast, pretreatment of CoQ10 significantly decreased ROS generation in the ONH astrocytes exposed to H2O2. In addition, H2O2-induced oxidative stress significantly decreased the cellular ATP level in the ONH astrocytes. However, pretreatment of CoQ10 significantly restored the cellular ATP level in the ONH astrocytes exposed to H2O2. Values are mean±S.D. *P<0.05 and **P<0.01 compared with vehicle-treated control ONH astrocytes or H2O2-treated ONH astrocytes. CoQ10, coenzyme Q10; H2O2, hydrogen peroxide
Mentions: To determine whether H2O2-induced oxidative stress alters mitochondrial bioenergetics in ONH astrocytes and whether CoQ10 treatment inhibits the alteration of mitochondrial bioenergetics, we measured cell viability, ROS generation and cellular ATP level. As shown in Figure 7, our findings show that H2O2-induced oxidative stress significantly decreased cell viability to 80.8±5.4% of the control value in the ONH astrocytes (P<0.05). However, pretreatment of CoQ10 significantly boosted cell viability to 92.6±4.6% in the ONH astrocytes exposed to H2O2 (P=0.001). In comparison with control ONH astrocytes, H2O2-induced oxidative stress significantly increased ROS generation by 7.82±0.81-fold over the control in the ONH astrocytes (P=0.01). In contrast, pretreatment of CoQ10 significantly decreased ROS generation to 4.67±0.83-fold of the control in the ONH astrocytes exposed to H2O2 (P<0.05). In addition, we found that H2O2-induced oxidative stress significantly decreased the cellular ATP level to 83.8±3.7% of the control value in the ONH astrocytes (P<0.01). However, pretreatment of CoQ10 nearly completely restored the cellular ATP level (96.9±4.3% of the control) in the ONH astrocytes exposed to H2O2 (P<0.05), suggesting that CoQ10 restores bioenergetic function in the ONH astrocytes to counter oxidative stress.

Bottom Line: In contrast, CoQ10 not only prevented activation of ONH astrocytes but also significantly decreased SOD2 and HO-1 protein expression in the ONH astrocytes against oxidative stress.Finally, oxidative stress triggered the upregulation of OXPHOS Cx protein expression, as well as reduction of cellular adeonsine triphosphate (ATP) production and increase of ROS generation in the ONH astocytes.However, CoQ10 preserved OXPHOS protein expression and cellular ATP production, as well as decreased ROS generation in the ONH astrocytes.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Optic Nerve Biology, Hamilton Glaucoma Center and Department of Ophthalmology, University of California, San Diego, La Jolla, CA, USA.

ABSTRACT
Oxidative stress contributes to dysfunction of glial cells in the optic nerve head (ONH). However, the biological basis of the precise functional role of mitochondria in this dysfunction is not fully understood. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain and a potent antioxidant, acts by scavenging reactive oxygen species (ROS) for protecting neuronal cells against oxidative stress in many neurodegenerative diseases. Here, we tested whether hydrogen peroxide (100 μM H2O2)-induced oxidative stress alters the mitochondrial network, oxidative phosphorylation (OXPHOS) complex (Cx) expression and bioenergetics, as well as whether CoQ10 can ameliorate oxidative stress-mediated alterations in mitochondria of the ONH astrocytes in vitro. Oxidative stress triggered the activation of ONH astrocytes and the upregulation of superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) protein expression in the ONH astrocytes. In contrast, CoQ10 not only prevented activation of ONH astrocytes but also significantly decreased SOD2 and HO-1 protein expression in the ONH astrocytes against oxidative stress. Further, CoQ10 prevented a significant loss of mitochondrial mass by increasing mitochondrial number and volume density and by preserving mitochondrial cristae structure, as well as promoted mitofilin and peroxisome-proliferator-activated receptor-γ coactivator-1 protein expression in the ONH astrocyte, suggesting an induction of mitochondrial biogenesis. Finally, oxidative stress triggered the upregulation of OXPHOS Cx protein expression, as well as reduction of cellular adeonsine triphosphate (ATP) production and increase of ROS generation in the ONH astocytes. However, CoQ10 preserved OXPHOS protein expression and cellular ATP production, as well as decreased ROS generation in the ONH astrocytes. On the basis of these observations, we suggest that oxidative stress-mediated mitochondrial dysfunction or alteration may be an important pathophysiological mechanism in the dysfunction of ONH astrocytes. CoQ10 may provide new therapeutic potentials and strategies for protecting ONH astrocytes against oxidative stress-mediated mitochondrial dysfunction or alteration in glaucoma and other optic neuropathies.

Show MeSH
Related in: MedlinePlus