5-ALA/SFC enhances HO-1 expression through the MAPK/Nrf2 antioxidant pathway and attenuates murine tubular epithelial cell apoptosis.
Chi LiuMasayuki FujinoShuoji ZhuYoshitaka IsakaHidenori ItoKiwamu TakahashiMotowo NakajimaTohru TanakaPing ZhuXiao-Kang LiPublished in: FEBS open bio (2019)
Cyclosporin A (CsA) is a common immunosuppressant, but its use is limited as it can cause chronic kidney injury. Oxidative stress and apoptosis play a key role in CsA-induced nephrotoxicity. This study investigated the protective effect of 5-aminolevulinic acid and iron (5-ALA/SFC) on CsA-induced injury in murine proximal tubular epithelial cells (mProx24). 5-ALA/SFC significantly inhibited apoptosis in CsA-treated mProx24 cells with increases in heme oxygenase (HO)-1, nuclear factor E2-related factor 2 (Nrf2), and p38, and Erk-1/2 phosphorylation. Moreover, 5-ALA/SFC suppressed production of reactive oxygen species in CsA-exposed cells and inhibition of HO-1 suppressed the protective effects of 5-ALA/SFC. In summary, 5-ALA/SFC may have potential for development into a treatment for the anti-nephrotoxic/apoptotic effects of CsA.
Keyphrases
- oxidative stress
- induced apoptosis
- cell cycle arrest
- diabetic rats
- pi k akt
- high glucose
- signaling pathway
- cell death
- nuclear factor
- endoplasmic reticulum stress
- cell proliferation
- ischemia reperfusion injury
- drug induced
- reactive oxygen species
- dna damage
- toll like receptor
- endothelial cells
- photodynamic therapy
- poor prognosis
- binding protein
- anti inflammatory
- climate change
- heat shock
- heat stress