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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 ameliorates oxidative stress in ONH astrocytes. (a) GFAP, SOD2 and HO-1 protein expression were significantly increased in the ONH astrocytes exposed to H2O2 (100 μM) compared with vehicle-treated control ONH astrocytes. In contrast, CoQ10 significantly reduced GFAP, SOD2 and HO-1 protein expression compared with ONH astrocytes exposed to H2O2. Relative intensity of chemiluminescence for each protein band was normalized using actin. Values are mean±S.D. *P<0.05 compared with vehicle-treated control ONH astrocytes or H2O2-treated ONH astrocytes. (b) Representative images show that SOD2 immunoreactivity was present in mitochondria of the ONH astrocytes. Of note, SOD2 immunoreactivity was increased in the ONH astrocytes exposed to H2O2. However, CoQ10 decreased SOD2 immunoreactivity in the ONH astrocytes exposed to H2O2. GFAP, glial fibrillary acidic protein; SOD2, superoxide dismutase 2; HO-1, heme oxygenase-1; CoQ10, coenzyme Q10; H2O2, hydrogen peroxide. Scale bars, 10 μm
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fig2: CoQ10 ameliorates oxidative stress in ONH astrocytes. (a) GFAP, SOD2 and HO-1 protein expression were significantly increased in the ONH astrocytes exposed to H2O2 (100 μM) compared with vehicle-treated control ONH astrocytes. In contrast, CoQ10 significantly reduced GFAP, SOD2 and HO-1 protein expression compared with ONH astrocytes exposed to H2O2. Relative intensity of chemiluminescence for each protein band was normalized using actin. Values are mean±S.D. *P<0.05 compared with vehicle-treated control ONH astrocytes or H2O2-treated ONH astrocytes. (b) Representative images show that SOD2 immunoreactivity was present in mitochondria of the ONH astrocytes. Of note, SOD2 immunoreactivity was increased in the ONH astrocytes exposed to H2O2. However, CoQ10 decreased SOD2 immunoreactivity in the ONH astrocytes exposed to H2O2. GFAP, glial fibrillary acidic protein; SOD2, superoxide dismutase 2; HO-1, heme oxygenase-1; CoQ10, coenzyme Q10; H2O2, hydrogen peroxide. Scale bars, 10 μm

Mentions: As reduction of oxidative stress has been proposed to be protective against glaucomatous damage,24, 25 we determined whether CoQ10 treatment prevents oxidative stress-mediated activation of ONH astrocytes in vitro using antibodies for GFAP, superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1). We observed that GFAP protein expression was significantly increased by 1.23±0.10-fold in the ONH astrocytes exposed to H2O2 (100 μM) compared with control cells exposed to vehicle. In contrast, CoQ10 significantly reduced GFAP protein expression by 0.97±0.08-fold in the ONH astrocytes exposed to H2O2 (Figure 2a). Intriguingly, we also found that SOD2 and HO-1 protein expression was significantly increased by 1.40±0.13- and 1.2±0.14-fold in the ONH astrocytes exposed to H2O2 compared with control cells, respectively. In contrast, CoQ10 significantly reduced SOD2 and HO-1 protein expression by 0.63±0.11- and 0.63±0.07-fold in the ONH astrocytes exposed to H2O2, respectively (Figure 2a). To determine whether oxidative stress alters SOD2 distribution and expression in the ONH astocytes, we performed immunocytochemistry in cultured ONH astrocytes using the antibody for SOD2. Consistently, we found that SOD2 immunoreactivity was present in the mitochondria of the ONH astrocytes. Moreover, we observed that ONH astrocytes exposed to H2O2 showed increase of SOD2 immunoreactivity in the mitochondria and cytoplasm compared with control cells. In contrast, CoQ10 decreased SOD2 immunoreactivity in the ONH astrocytes exposed to H2O2 (Figure 2b). These results indicate that CoQ10 prevents activation of ONH astrocytes by blocking 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 ameliorates oxidative stress in ONH astrocytes. (a) GFAP, SOD2 and HO-1 protein expression were significantly increased in the ONH astrocytes exposed to H2O2 (100 μM) compared with vehicle-treated control ONH astrocytes. In contrast, CoQ10 significantly reduced GFAP, SOD2 and HO-1 protein expression compared with ONH astrocytes exposed to H2O2. Relative intensity of chemiluminescence for each protein band was normalized using actin. Values are mean±S.D. *P<0.05 compared with vehicle-treated control ONH astrocytes or H2O2-treated ONH astrocytes. (b) Representative images show that SOD2 immunoreactivity was present in mitochondria of the ONH astrocytes. Of note, SOD2 immunoreactivity was increased in the ONH astrocytes exposed to H2O2. However, CoQ10 decreased SOD2 immunoreactivity in the ONH astrocytes exposed to H2O2. GFAP, glial fibrillary acidic protein; SOD2, superoxide dismutase 2; HO-1, heme oxygenase-1; CoQ10, coenzyme Q10; H2O2, hydrogen peroxide. Scale bars, 10 μm
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fig2: CoQ10 ameliorates oxidative stress in ONH astrocytes. (a) GFAP, SOD2 and HO-1 protein expression were significantly increased in the ONH astrocytes exposed to H2O2 (100 μM) compared with vehicle-treated control ONH astrocytes. In contrast, CoQ10 significantly reduced GFAP, SOD2 and HO-1 protein expression compared with ONH astrocytes exposed to H2O2. Relative intensity of chemiluminescence for each protein band was normalized using actin. Values are mean±S.D. *P<0.05 compared with vehicle-treated control ONH astrocytes or H2O2-treated ONH astrocytes. (b) Representative images show that SOD2 immunoreactivity was present in mitochondria of the ONH astrocytes. Of note, SOD2 immunoreactivity was increased in the ONH astrocytes exposed to H2O2. However, CoQ10 decreased SOD2 immunoreactivity in the ONH astrocytes exposed to H2O2. GFAP, glial fibrillary acidic protein; SOD2, superoxide dismutase 2; HO-1, heme oxygenase-1; CoQ10, coenzyme Q10; H2O2, hydrogen peroxide. Scale bars, 10 μm
Mentions: As reduction of oxidative stress has been proposed to be protective against glaucomatous damage,24, 25 we determined whether CoQ10 treatment prevents oxidative stress-mediated activation of ONH astrocytes in vitro using antibodies for GFAP, superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1). We observed that GFAP protein expression was significantly increased by 1.23±0.10-fold in the ONH astrocytes exposed to H2O2 (100 μM) compared with control cells exposed to vehicle. In contrast, CoQ10 significantly reduced GFAP protein expression by 0.97±0.08-fold in the ONH astrocytes exposed to H2O2 (Figure 2a). Intriguingly, we also found that SOD2 and HO-1 protein expression was significantly increased by 1.40±0.13- and 1.2±0.14-fold in the ONH astrocytes exposed to H2O2 compared with control cells, respectively. In contrast, CoQ10 significantly reduced SOD2 and HO-1 protein expression by 0.63±0.11- and 0.63±0.07-fold in the ONH astrocytes exposed to H2O2, respectively (Figure 2a). To determine whether oxidative stress alters SOD2 distribution and expression in the ONH astocytes, we performed immunocytochemistry in cultured ONH astrocytes using the antibody for SOD2. Consistently, we found that SOD2 immunoreactivity was present in the mitochondria of the ONH astrocytes. Moreover, we observed that ONH astrocytes exposed to H2O2 showed increase of SOD2 immunoreactivity in the mitochondria and cytoplasm compared with control cells. In contrast, CoQ10 decreased SOD2 immunoreactivity in the ONH astrocytes exposed to H2O2 (Figure 2b). These results indicate that CoQ10 prevents activation of ONH astrocytes by blocking 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