Publication: Unripe carica papaya protects methylglyoxal-invoked endothelial cell inflammation and apoptosis via the suppression of oxidative stress and AKt/MAPK/NF-κB signals
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Issued Date
2021
Resource Type
Language
eng
File Type
application/pdf
ISSN
20763921
Other identifier(s)
2-s2.0-85110721551
Rights Holder(s)
มหาวิทยาลัยศรีนครินทรวิโรฒ
Bibliographic Citation
Antioxidants. Vol 10, No.8 (2021)
Suggested Citation
Jarisarapurin W., Kunchana K., Chularojmontri L., Wattanapitayakul S.K. Unripe carica papaya protects methylglyoxal-invoked endothelial cell inflammation and apoptosis via the suppression of oxidative stress and AKt/MAPK/NF-κB signals. Antioxidants. Vol 10, No.8 (2021). doi:10.3390/antiox10081158 Retrieved from: https://hdl.handle.net/20.500.14740/5785
Abstract
Methylglyoxal (MGO), a highly reactive dicarbonyl compound, causes endothelial oxida-tive stress and vascular complications in diabetes. Excessive MGO-induced ROS production triggers eNOS uncoupling, inflammatory responses, and cell death signaling cascades. Our previous study reported that unripe Carica papaya (UCP) had antioxidant activities that prevented H2 O2-induced endothelial cell death. Therefore, this study investigated the preventive effect of UCP on MGO-induced endothelial cell damage, inflammation, and apoptosis. The human endothelial cell line (EA.hy926) was pretreated with UCP for 24 h, followed by MGO-induced dicarbonyl stress. Treated cells were evaluated for intracellular ROS/O2•− formation, cell viability, apoptosis, NO releases, and cell signaling through eNOS, iNOS, COX-2, NF-κB, Akt, MAPK (JNK and p38), and AMPK/SIRT1 autophagy pathways. UCP reduced oxidative stress and diminished phosphorylation of Akt, stress-activated MAPK, leading to the decreases in NF-kB-activated iNOS and COX-2 expression. However, UCP had no impact on the autophagy pathway (AMPK and SIRT1). Although UCP pretreatment decreased eNOS phosphorylation, the amount of NO production was not altered. The signaling of eNOS and NO production were decreased after MGO incubation, but these effects were unaffected by UCP pretreatment. In summary, UCP protected endothelial cells against carbonyl stress by the mechanisms related to ROS/O2•− scavenging activities, suppression of inflammatory signaling, and inhibition of JNK/p38/apoptosis pathway. Thus, UCP shows considerable promise for developing novel functional food and nutraceutical products to reduce risks of endothelial inflammation and vascular complications in diabetes. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.