Protective effect of diphlorethohydroxycarmalol against oxidative stress-induced DNA damage and apoptosis in retinal pigment epithelial cells

Park, Cheol; Lee, Hyesook; Hong, Su Hyun; Kim, Jeong‐Hwan; Park, Seh-Kwang; Jeong, Jong Ok; Kim, Gi‐Young; Hyun, Jin Won; Yun, Seok Joong; Kim, Byung Woo; Kim, Wun-Jae; Choi, Yung Hyun

doi:10.1080/15569527.2019.1613425

Cited by 30 publications

(22 citation statements)

References 55 publications

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“…In RPE cells, oxidative stress by ROS generation is mainly derived from the photo-oxidation of mitochondria, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and the decline in ability to repair damaged organelles [23,43,44]. Several studies have suggested that H 2 O 2 enhances the production of intracellular ROS in ARPE-19 cells [26,45,46], and our results agree with these reports (Figure 4). Of note, spermidine does not block H 2 O 2 -induced intracellular ROS generation despite its antioxidant actions.…”

Section: Discussionsupporting

confidence: 91%

Spermidine Attenuates Oxidative Stress-Induced Apoptosis via Blocking Ca2+ Overload in Retinal Pigment Epithelial Cells Independently of ROS

Kim

Kim²,

Hwangbo

et al. 2021

IJMS

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Retinal pigment epithelial (RPE) cells occupy the outer layer of the retina and perform various biological functions. Oxidative damage to RPE cells is a major risk factor for retinal degeneration that ultimately leads to vision loss. In this study, we investigated the role of spermidine in a hydrogen peroxide (H2O2)-induced oxidative stress model using human RPE cells. Our findings showed that 300 μM H2O2 increased cytotoxicity, apoptosis, and cell cycle arrest in the G2/M phase, whereas these effects were markedly suppressed by 10 μM spermidine. Furthermore, spermidine significantly reduced H2O2-induced mitochondrial dysfunction including mitochondrial membrane potential and mitochondrial activity. Although spermidine displays antioxidant properties, the generation of intracellular reactive oxygen species (ROS) upon H2O2 insult was not regulated by spermidine. Spermidine did suppress the increase in cytosolic Ca2+ levels resulting from endoplasmic reticulum stress in H2O2-stimulated human RPE cells. Treatment with a cytosolic Ca2+ chelator markedly reversed H2O2-induced cellular dysfunction. Overall, spermidine protected against H2O2-induced cellular damage by blocking the increase of intracellular Ca2+ independently of ROS. These results suggest that spermidine protects RPE cells from oxidative stress, which could be a useful treatment for retinal diseases.

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Section: Discussionsupporting

confidence: 91%

Spermidine Attenuates Oxidative Stress-Induced Apoptosis via Blocking Ca2+ Overload in Retinal Pigment Epithelial Cells Independently of ROS

Kim

Kim²,

Hwangbo

et al. 2021

IJMS

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“…Several studies have shown that naturally-occurring compounds inhibit oxidative stress-induced RPE cell damage through enhancing antioxidant activity and anti-apoptotic function [ 41 , 42 ]. For both RP and DR, botanical compounds and plant extracts may have significant effects on treatment and prevention [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…Efficient treatment of RP can be antioxidant agents and autophagy modulators, which curtails the excessive ROS levels and regulates autophagy [ 40 ]. Diphlorethohydroxycarmalol and kaemperol protect RPE cells from oxidative stress-induced DNA damage and apoptosis [ 41 , 42 ]. Curcumin inhibits N-methyl-N-nitrosourea-induced photoreceptor cell apoptosis by attenuating DNA oxidative stress, indicating that curcumin may inhibit the onset and progression of human RP [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Eucalyptol Inhibits Amyloid-β-Induced Barrier Dysfunction in Glucose-Exposed Retinal Pigment Epithelial Cells and Diabetic Eyes

et al. 2020

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Hyperglycemia elicits tight junction disruption and blood-retinal barrier breakdown, resulting in diabetes-associated vison loss. Eucalyptol is a natural compound found in eucalyptus oil with diverse bioactivities. This study evaluated that eucalyptol ameliorated tight junctions and retinal barrier function in glucose/amyloid-β (Aβ)-exposed human retinal pigment epithelial (RPE) cells and in db/db mouse eyes. RPE cells were cultured in media containing 33 mM glucose or 5 μM Aβ for 4 days in the presence of 1–20 μM eucalyptol. The in vivo animal study employed db/db mice orally administrated with 10 mg/kg eucalyptol. Nontoxic eucalyptol inhibited the Aβ induction in glucose-loaded RPE cells and diabetic mouse eyes. Eucalyptol reversed the induction of tight junction-associated proteins of ZO-1, occludin-1 and matrix metalloproteinases in glucose- or Aβ-exposed RPE cells and in diabetic eyes, accompanying inhibition of RPE detachment from Bruch’s membrane. Adding eucalyptol to glucose- or Aβ-loaded RPE cells, and diabetic mouse eyes reciprocally reversed induction/activation of apoptosis-related bcl-2, bax, cytochrome C/Apaf-1 and caspases. Eucalyptol attenuated the generation of reactive oxygen species and the induction of receptor for advanced glycation end products in Aβ-exposed RPE cells and diabetic eyes. Eucalyptol may ameliorate RPE barrier dysfunction in diabetic eyes through counteracting Aβ-mediated oxidative stress-induced RPE cell apoptosis.

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“…The extent of the DNA breaks in apoptotic cells was evaluated using the TUNEL staining kit (Promega, Madison, WI, USA) [49]. In brief, cells were seeded onto glass coverslips in 4-well and treated with coptisine for 24 h. The cells were fixed with 4% methanol-free formaldehyde solution for 25 min, and then subjected to TUNEL assay, according to the manufacturer's instructions.…”

Section: Tunel Assaymentioning

confidence: 99%

Induction of Apoptosis by Coptisine in Hep3B Hepatocellular Carcinoma Cells through Activation of the ROS-Mediated JNK Signaling Pathway

Kim

Hwangbo

Lee

et al. 2020

IJMS

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Hepatocellular carcinoma (HCC) has a high mortality rate worldwide, and treatment is very limited due to its high recurrence and low diagnosis rate, and therefore there is an increasing need to develop more effective drugs to treat HCC. Coptisine is one of the isoquinoline alkaloids, and it has various pharmacological effects. However, the evidence for the molecular mechanism of the anticancer efficacy is still insufficient. Therefore, this study investigated the antiproliferative effect of coptisine on human HCC Hep3B cells and identified the action mechanism. Our results showed that coptisine markedly increased DNA damage and apoptotic cell death, which was associated with induction of death receptor proteins. Coptisine also significantly upregulated expression of proapoptotic Bax protein, downregulated expression of anti-apoptotic Bcl-2 protein, and activated caspase-3, -8, and -9. In addition, coptisine remarkably increased the generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential (MMP), and release of cytochrome c into the cytoplasm. However, N-acetylcysteine (NAC), a ROS scavenger, significantly attenuated the apoptosis-inducing effect of coptisine. It is worth noting that coptisine significantly upregulated phosphorylation of ROS-dependent c-Jun N-terminal kinase (JNK), whereas treatment with JNK inhibitor could suppress an apoptosis-related series event. Taken together, our results suggest that coptisine has an anticancer effect in Hep3B cells through ROS-mediated activation of the JNK signaling pathway.

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Protective effect of diphlorethohydroxycarmalol against oxidative stress-induced DNA damage and apoptosis in retinal pigment epithelial cells

Cited by 30 publications

References 55 publications

Spermidine Attenuates Oxidative Stress-Induced Apoptosis via Blocking Ca2+ Overload in Retinal Pigment Epithelial Cells Independently of ROS

Spermidine Attenuates Oxidative Stress-Induced Apoptosis via Blocking Ca2+ Overload in Retinal Pigment Epithelial Cells Independently of ROS

Eucalyptol Inhibits Amyloid-β-Induced Barrier Dysfunction in Glucose-Exposed Retinal Pigment Epithelial Cells and Diabetic Eyes

Induction of Apoptosis by Coptisine in Hep3B Hepatocellular Carcinoma Cells through Activation of the ROS-Mediated JNK Signaling Pathway

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