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

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

doi:10.3390/ijms22041577

Open AccessArticle

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

by

Charng-Cherng Chyau

^1,*

,

Huei-Lin Wu

¹,

Chiung-Chi Peng

²,

Shiau-Huei Huang

¹,

Chin-Chu Chen

³,

Cheng-Hsu Chen

⁴

and

Robert Y. Peng

^1,*

¹

Research Institute of Biotechnology, Hungkuang University, Taichung 43302, Taiwan

²

Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan

³

Grape King Biotechnology Center, Chung-Li City 320054, Taiwan

⁴

Department of Nephrology, Taichung Veterans General Hospital, Taichung 40705, Taiwan

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2021, 22(4), 1577; https://doi.org/10.3390/ijms22041577

Submission received: 14 January 2021 / Revised: 31 January 2021 / Accepted: 1 February 2021 / Published: 4 February 2021

(This article belongs to the Special Issue Natural Antioxidants in Cell Signaling)

Download

Browse Figures

Versions Notes

Abstract

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.

Keywords: endoplasmic reticulum (ER); oxidative stress; renal HK–2 cells; diclofenac; meloxicam

Share and Cite

MDPI and ACS Style

Chyau, C.-C.; Wu, H.-L.; Peng, C.-C.; Huang, S.-H.; Chen, C.-C.; Chen, C.-H.; Peng, R.Y. 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. Int. J. Mol. Sci. 2021, 22, 1577. https://doi.org/10.3390/ijms22041577

AMA Style

Chyau C-C, Wu H-L, Peng C-C, Huang S-H, Chen C-C, Chen C-H, Peng RY. 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. International Journal of Molecular Sciences. 2021; 22(4):1577. https://doi.org/10.3390/ijms22041577

Chicago/Turabian Style

Chyau, Charng-Cherng, Huei-Lin Wu, Chiung-Chi Peng, Shiau-Huei Huang, Chin-Chu Chen, Cheng-Hsu Chen, and Robert Y. Peng. 2021. "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" International Journal of Molecular Sciences 22, no. 4: 1577. https://doi.org/10.3390/ijms22041577

APA Style

Chyau, C.-C., Wu, H.-L., Peng, C.-C., Huang, S.-H., Chen, C.-C., Chen, C.-H., & Peng, R. Y. (2021). 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. International Journal of Molecular Sciences, 22(4), 1577. https://doi.org/10.3390/ijms22041577

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

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

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI