Effects of &lt;smlcap&gt;L&lt;/smlcap&gt;-Carnitine on High Glucose-Induced Oxidative Stress in Retinal Ganglion Cells

Cao, Yu; Li, Xin; Shi, Ping; Wang, Lexin; Sui, Zhongguo

doi:10.1159/000363062

Cited by 29 publications

(28 citation statements)

References 32 publications

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“…The results revealed that RPE proliferative ability is inhibited by glucose in a dose dependent manner. In addition, ROS generation is also induced by glucose in a dose dependent manner (Figure 1J-K), which is in accordance with the previous studies [34, 35].…”

Section: Discussionsupporting

confidence: 92%

High-glucose Induces Retinal Pigment Epithelium Mitochondrial Pathways of Apoptosis and Inhibits Mitophagy by Regulating ROS/PINK1/Parkin Signal Pathway

Yang¹,

Yuan

et al. 2018

Preprint

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Diabetic retinopathy (DR) caused visual performance degradation seriously endangers human beings’ health, uncovering the underlying mechanism might shed light on the discovery of DR therapeutic treatments. In this study, we found that the effects of glucose on retinal pigment epithelium (RPE) varies in a dose dependent manner, high-glucose promotes ROS generation and cell apoptosis, inhibits mitophagy as well as proliferative abilities, while low-glucose induces ROS production and cell mitophagy, but has little impacts on cell apoptosis and proliferation. Of note, the toxic effects of high-glucose on RPE are alleviated by ROS scavengers and aggravated by autophagy inhibitor 3-methyladenine (3-MA) or mitophagy inhibitor cyclosporin A (CsA). High-glucose induced ROS generation is merely eliminated by ROS scavengers instead of mitophagy or autophagy inhibitor. We also proved that high-glucose inhibits cell proliferation and promotes cell apoptosis by regulating ROS mediated inhibition of mitophagy. In addition, mitophagy associated proteins PINK1 and Parkin are downregulated by high-glucose or hydrogen peroxide treatments, which are reversed by ROS scavengers. Of note, Knock-down of PINK1 decreases phospharylated Parkin instead of total Parkin levels in RPE. Intriguingly, high-glucose’s inhibiting effects on cell mitophagy as well as proliferation and its promoting effects on cell apoptosis are reversed by either PINK1 or Parkin overexpression. Therefore, we concluded that high-glucose promotes RPE apoptosis and inhibits cell proliferation as well as mitophagy by regulating oxidative stress mediated inactivation of ROS/PINKl/Parkin signal pathway.

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Section: Discussionsupporting

confidence: 92%

High-glucose Induces Retinal Pigment Epithelium Mitochondrial Pathways of Apoptosis and Inhibits Mitophagy by Regulating ROS/PINK1/Parkin Signal Pathway

Yang¹,

Yuan

et al. 2018

Preprint

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“…The generation of ROS under high glucose stress conditions has been established in many cell types [ 27 , 28 ]. When the ROS level exceeds the capacity of the antioxidant defense system, ROS initiates chain reactions by oxidizing cellular macromolecules like lipids and proteins, which in turn interrupts cellular activities, ultimately causing apoptosis [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Hesperidin (Citrus Flavonone) on High Glucose Induced Oxidative Stress and Apoptosis in a Cellular Model for Diabetic Retinopathy

et al. 2017

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The aim of this study was to investigate the protective effects and mechanisms of hesperidin, a plant based active flavanone found in citrus fruits, under the oxidative stress and apoptosis induced by high levels of glucose in retinal ganglial cells (RGCs). RGC-5 cells were pretreated with hesperidin (12.5, 25, or 50 μmol/L) for 6 h followed by exposure to high (33.3 mmol/L) d-glucose for 48 h. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was adopted to evaluate cell viability. Mitochondrial function was estimated by measuring the mitochondrial membrane potential (ΔΨm). A fluorescent probe was employed to evaluate the intercellular production of reactive oxygen species (ROS). Colorimetric assay kits were used to evaluate lipid peroxidation, antioxidant enzyme activities, and protein carbonyls formation. The expression of apoptosis-related proteins and mitogen-activated protein kinase (MAPK) were measured with Western blotting. Hesperidin inhibited high glucose-mediated cell loss and restored mitochondrial function including a reversion of ΔΨm loss and cytochrome c release. Treated with hesperidin, high glucose-induced increase in ROS, malondialdehyde, and protein carbonyl levels were blocked in RGC-5 cells. Hesperidin was found to elevate the activities of superoxide dismutase, catalase, glutathione peroxidase, and to recover glutathione levels. Hesperidin inhibited high glucose-induced cell apoptosis by attenuating the downregulation of caspase-9, caspase-3, and Bax/Bcl-2. Furthermore, the phosphorylation of c-Jun N-terminal kinases (JNK) and p38 MAPK triggered by high glucose were attenuated in RGC-5 cells after their incubation with hesperdin. We concluded that hesperidin may protect RGC-5 cells from high glucose-induced injury since it owns the properties of antioxidant action and blocks mitochondria-mediated apoptosis.

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“…It has been widely reported that Hax-1 interacts with apoptosis-associated proteins, including HtrA2, protease-activated receptor 1 (Par1), caspase-3, caspase-9 or Bcl-2-associated X protein (8,(21)(22)(23). Numerous studies have demonstrated that the activation of caspase-3 was the key effector of RGC apoptosis following ONC (24)(25)(26). Previously, Hax-1 has been identified as a new substrate of caspase-3, which prevents apoptosis by inhibiting the catalytic activation of caspase-3 (27).…”

Section: Discussionmentioning

confidence: 99%

Alterations in the expression of Hs1-associated protein X-1 in the rat retina after optic nerve crush

Cui

et al. 2016

Molecular Medicine Reports

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HS-1-associated protein X-1 (Hax-1) has been suggested to be expressed in various rodent and human tissues. Accumulating evidence has demonstrated that Hax‑1 exerts an anti‑apoptotic effect in neurological diseases. Furthermore, it has also been reported that Hax‑1 interacts with various apoptosis‑associated proteins, including high temperature-regulated A2 (HtrA2) and caspase‑3. Previous studies have indicated that abnormal expression of Hax‑1 may be associated with the development of the nervous system and with the pathophysiology of neurological diseases, including traumatic brain injury and cerebral ischemia. The present study reported temporal‑spatial patterns of Hax‑1 in rat retina following optic nerve crush (ONC). Using western blotting and double‑immunofluorescence, significant upregulation of Hax‑1 was observed in retinal ganglion cells (RGCs) in the retina following ONC. Increased Hax‑1 expression was demonstrated to be accompanied by upregulation of active‑caspase‑3 and HtrA2 following ONC. In addition, Hax-1 co‑localized with active caspase‑3 and HtrA2 in RGCs following ONC. Terminal deoxynucleotidyl transferase‑mediated biotinylated-dUTP nick‑end labeling staining suggested that Hax‑1 was involved in RGC apoptosis following ONC. Thus, these results suggested that Hax‑1 may participate in regulating RGC apoptosis via interacting with caspase‑3 and HtrA2 following ONC.

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Effects of <smlcap>L</smlcap>-Carnitine on High Glucose-Induced Oxidative Stress in Retinal Ganglion Cells

Cited by 29 publications

References 32 publications

High-glucose Induces Retinal Pigment Epithelium Mitochondrial Pathways of Apoptosis and Inhibits Mitophagy by Regulating ROS/PINK1/Parkin Signal Pathway

High-glucose Induces Retinal Pigment Epithelium Mitochondrial Pathways of Apoptosis and Inhibits Mitophagy by Regulating ROS/PINK1/Parkin Signal Pathway

Protective Effects of Hesperidin (Citrus Flavonone) on High Glucose Induced Oxidative Stress and Apoptosis in a Cellular Model for Diabetic Retinopathy

Alterations in the expression of Hs1-associated protein X-1 in the rat retina after optic nerve crush

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