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EGCG protects against 6‐OHDA induced neurotoxicity in a cell culture model
Author(s) -
Chen Dan,
Kanthasamy Anumantha G,
Reddy Manju B
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.255.5
Subject(s) - neurotoxicity , dmt1 , hepcidin , ferroportin , transferrin receptor , chemistry , ferritin , cystatin c , neurodegeneration , pharmacology , transferrin , toxicity , transporter , medicine , biochemistry , biology , inflammation , gene , disease , organic chemistry , renal function
Disruption of iron metabolism may involve in the progression of Parkinson's disease. Our objective was to test whether the protective effect of (−)‐epigallocatechin‐3‐gallate (EGCG) against 6‐hydroxydopamine (6‐OHDA) induced neurotoxicity was by regulating iron homeostasis in N27 cells. EGCG pretreatment significantly protected against 6‐OHDA‐induced neurotoxicity (MTT, SYTOX Green and Caspase‐3 activity assays). EGCG with 6OHDA treatment significantly increased (p<0.0001) TH+ cell count (3.1‐fold) and neurite length (12.5‐fold) compared with 6‐OHDA alone in primary mesencephalic neurons. 6‐OHDA treatment significantly (p<0.05) increased divalent metal transporter‐1 (DMT1), hepcidin, transferrin receptor‐2 (TfR2), H‐ferritin and decreased ferroportin‐1 (Fpn1), TfR1 mRNA expressions. The protein expressions of DMT1, hepcidin and Fpn1 matched with the gene expression data. However, EGCG significantly reversed the effect of 6‐OHDA on above genes and proteins expression. The increased ~2‐fold (p<0.001) 55 Fe cell uptake with 6‐OHDA and normalization with EGCG pretreatment confirmed iron burden associated with neurotoxicity and protection by EGCG. In conclusion, EGCG protected against 6‐OHDA induced neurotoxicity by regulating genes and proteins involved in brain iron homeostasis. However, further studies are warranted to determine the mechanism of that regulation. Grant Funding Source : Nutrition Wellness and Research Center