Conditioned media of choroid plexus epithelial cells induces Nrf2-activated phase II antioxidant response proteins and suppresses oxidative stress-induced apoptosis in PC12 cells.
Based on the critical role of the choroid plexus (CP) in detoxification processes in the central nervous system (CNS), herein we investigated the effect of choroid plexus epithelial cells conditioned media (CPECs-CM) under oxidative conditions. CPECs were isolated from rat brains, cultured, and the conditioned media were collected. Then pheochromocytoma neuron-like cells (PC12) were treated simultaneously with CPECs-CM and H2O2 as the oxidative stressor. Next, the effect of CPECs-CM on neurite outgrowth and cell differentiation in the presence of H2O2 was determined. Our results showed that CPECs-CM improved the expansion of neurites and differentiation in PC12 cells under oxidative stress conditions. Changes in apoptotic factors, nuclear factor erythroid 2-related factor 2 (Nrf2) and γ-glutamylcysteine synthetase as the highlighted pathway in the antioxidant defense system were determined by western blot. Also, the activity of antioxidant enzymes and lipid peroxidation level were determined. CPECs-CM-treated PC12 cells could survive after exposure to H2O2 by reduction of caspase-3 cleavage and Bax level and elevation of anti-apoptotic factor Bcl2. Our data also revealed that Nrf2 activation, and consequently its downstream protein levels, increased in the presence of CPECs-CM. Based on our data, we can conclude that CPECs-CM protects PC12 cells against oxidative stress and apoptosis. It seems that CPECs secrete antioxidative agents and neurotrophic factors that have a role in the health of the CNS.
NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abbas
A
Aliaghaei
Fariba
F
Khodagholi
Abolhassan
A
Ahmadiani
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000166:cytology*; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004847:Epithelial Cells / Q000378:metabolism*; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D050217:Metabolic Detoxication, Phase II; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar
D017077:Culture Media, Conditioned; D051267:NF-E2-Related Factor 2; D005721:Glutamate-Cysteine Ligase