Albumin evokes Ca 2+ -induced cell oxidative stress and apoptosis through TRPM2 channel in renal collecting duct cells reduced by curcumin
- Nazıroğlu, Mustafa Neuroscience Research Center, Suleyman Demirel University, Isparta, Turkey - Department of Biophysics, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey - Department of Neuroscience, Health Science Institute, Suleyman Demirel University, Isparta, Turkey
- Çiğ, Bilal Department of Biophysics, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey - Department of Neuroscience, Health Science Institute, Suleyman Demirel University, Isparta, Turkey
- Yazğan, Yener Department of Biophysics, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey - Department of Neuroscience, Health Science Institute, Suleyman Demirel University, Isparta, Turkey
- Schwaerzer, Gerburg K. Institute of Anatomy, Christian-Albrechts-University of Kiel, Kiel, Germany
- Theilig, Franziska Institute of Anatomy, Christian-Albrechts-University of Kiel, Kiel, Germany - Anatomy, Department of Medicine, University of Fribourg, Fribourg, Switzerland
- Pecze, László Anatomy, Department of Medicine, University of Fribourg, Fribourg, Switzerland - Independent Scientist, Neuchhatel, Switzerland
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27.08.2019
Published in:
- Scientific Reports. - 2019, vol. 9, no. 1, p. 1–16
English
In proteinuric nephropathies of chronic kidney disease, the epithelial cells of the nephron including the collecting duct are exposed to high concentrations of luminal albumin. Albumin is taken up from collecting duct cells by endocytosis causing excessive reactive oxygen species (ROS) production and a proinflammatory response. Curcumin used in the traditional medicine possesses anti-inflammatory and antioxidant effects. ROS and ADP-ribose (ADPR) activate the cation channel TRPM2. We hypothesize, that albumin-induced cell stress and proinflammatory response are mediated by Ca2+ and can be reduced by curcumin. The cortical collecting duct (CCD) cells mpkCCDc14 exhibit spontaneous and inducible Ca2+ oscillations, which can be blocked by pre-treatment with curcumin. Curcumin accumulates in plasma membrane and intracellular vesicles, where it interferes with TRPM2 and decreases the influx of Ca2+. Albumin reduces cell viability and increases apoptosis, NF-κB activation, and mitochondrial membrane depolarization via Ca2+-dependent signaling, which results in increased ROS production. Albumin-induced cell stress is diminished by the inhibition of TRPM2 after administration of curcumin and ADPR (PARP1) inhibitors. Curcumin did not reduce the Ca2+ elevation induced by thapsigargin in Ca2+-free medium, but it reduced the function of store-operated Ca2+ channels and ATP-evoked Ca2+ response. In conclusion, albumin-induced oxidative stress is mediated by Ca2+-dependent signaling via TRPM2 and leads to cell damage and a proinflammatory response, strengthening the role of CCD cells in the progression of chronic kidney disease.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Médecine
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 327434
- DOI 10.1038/s41598-019-48716-x
- Persistent URL
- https://folia.unifr.ch/unifr/documents/308248
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