Potential protection effect of er homeostasis of n6-(2-hydroxyethyl)adenosine isolated from cordyceps cicadae in nonsteroidal anti-inflammatory drug-stimulated human proximal tubular cells

Charng Cherng Chyau, Huei Lin Wu, Chiung Chi Peng, Shiau Huei Huang, Chin Chu Chen, Cheng Hsu Chen, Robert Y. Peng

研究成果: 雜誌貢獻文章同行評審

摘要

Nonsteroidal anti-inflammatory drugs (NSAIDs) belong to a class of universally and commonly used anti-inflammatory analgesics worldwide. A diversity of drawbacks of NSAIDs have been reported including cellular oxidative stress, which in turn triggers the accumulation of unfolded proteins, enhancing endoplasmic reticulum stress, and finally resulting in renal cell damage. Cordyceps cicadae (CC) has been used as a traditional medicine for improving renal function via its anti-inflammatory effects. N6-(2-hydroxyethyl)adenosine (HEA), a physiologically active compound, has been reported from CC mycelia (CCM) with anti-inflammatory effects. We hypothesize that HEA could protect human proximal tubular cells (HK−2) from NSAID-mediated effects on differential gene expression at the mRNA and protein levels. To verify this, we first isolated HEA from CCM using Sephadex® LH−20 column chromatography. The MTT assay revealed HEA to be nontoxic up to 100 µM toward HK−2 cells. The HK−2 cells were pretreated with HEA (10–20 µM) and then insulted with the NSAIDs diclofenac (DCF, 200 µM) and meloxicam (MXC, 400 µM) for 24 h. HEA (20 µM) effectively prevented ER stress by attenuating ROS production (p < 0.001) and gene expression of ATF−6, PERK, IRE1α, CDCFHOP, IL1β, and NFκB within 24 h. Moreover, HEA reversed the increase of GRP78 and CHOP protein expression levels induced by DCF and MXC, and restored the ER homeostasis. These results demonstrated that HEA treatments effectively protect against DCF-and MXC-induced ER stress damage in human proximal tubular cells through regulation of the GRP78/ATF6/PERK/IRE1α/CHOP pathway.
原文英語
文章編號1577
頁(從 - 到)1-17
頁數17
期刊International journal of molecular sciences
22
發行號4
DOIs
出版狀態已發佈 - 二月 2021

ASJC Scopus subject areas

  • 催化
  • 分子生物學
  • 光譜
  • 電腦科學應用
  • 物理與理論化學
  • 有機化學
  • 無機化學

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