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- Title
Indole-6-Carboxaldehyde Isolated from Sargassum thunbergii (Mertens) Kuntze Prevents Oxidative Stress-Induced Cellular Damage in V79-4 Chinese Hamster Lung Fibroblasts through the Activation of the Nrf2/HO-1 Signaling Pathway.
- Authors
Sung Ok Kim; Yung Hyun Choi
- Abstract
Background/Aims: The disruption of redox equilibrium by oxidative stress, which is characterized by an overproduction of reactive oxygen species (ROS), is considered to be associated with fibroblast death in severe lung diseases. Indole-6-carboxaldehyde (I6CA) is a natural indole derivative isolated from Sargassum thunbergii, which a type of brown algae. However, the antioxidative effects of I6CA, and their mechanisms, have not been identified. This study was conducted to investigate the potential protective effects of I6CA against oxidative stress in V79-4 Chinese hamster lung fibroblasts. Methods: Cell viability and mechanisms related to antioxidant activity of I6CA (ROS production, cell cycle, DNA damage, mitochondrial membrane potential (MMP) and apoptosis) were studied. Western blot analysis was carried out to understand the involvement of various genes at protein level. Results: Our results demonstrated that I6CA inhibited hydrogen peroxide (H2O2)-induced cytotoxicity by blocking abnormal ROS accumulation. H2O2 treatment of V79-4 fibroblasts caused cell cycle arrest at the G2/M phase, which was accompanied by increased expression of the cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1 and decreased expression of cyclin B1 and cyclin A. However, these effects were attenuated by treatment with I6CA. I6CA also effectively protected V79-4 cells against H2O2-induced apoptosis by increasing the Bcl-2/Bax ratio and suppressing the loss of MMP and the cytosolic release of cytochrome c. In addition, the activation of nuclear factor-erythroid-2-related factor 2 (Nrf2) was markedly promoted by I6CA, which was associated with enhanced expression and activity of heme oxygenase-1 (HO-1). However, inhibiting the activity of HO-1 by zinc protoporphyrin IX, a potent inhibitor of HO-1, eliminated the ROS scavenging and anti-apoptotic effects of I6CA, indicating that I6CA was able to protect V79-4 lung fibroblasts from H2O2-induced oxidative stress by activating the Nrf2 signaling pathway. Conclusion: We suggest that I6CA may be useful as a candidate therapeutic agent for the treatment of oxidative stress-related lung diseases.
- Subjects
SARGASSUM; OXIDATIVE stress; APOPTOSIS; DNA damage; CYTOCHROMES
- Publication
Cellular Physiology & Biochemistry (Cell Physiol Biochem Press GmbH & Co. KG), 2020, Vol 54, Issue 5, p959
- ISSN
1015-8987
- Publication type
Academic Journal
- DOI
10.33594/000000281