TY - JOUR
T1 - Curcumin protects against NMDA-induced toxicity
T2 - A possible role for NR2A subunit
AU - Matteucci, Andrea
AU - Cammarota, Roberta
AU - Paradisi, Silvia
AU - Varano, Monica
AU - Balduzzi, Maria
AU - Leo, Lanfranco
AU - Bellenchi, Gian C.
AU - de Nuccio, Chiara
AU - Carnovale-Scalzo, Giovanna
AU - Scorcia, Giovanni
AU - Frank, Claudio
AU - Mallozzi, Cinzia
AU - di Stasi, Annamaria M.
AU - Visentin, Sergio
AU - Malchiodi-Albedi, Fiorella
PY - 2011/2
Y1 - 2011/2
N2 - PURPOSE. Curcumin, a phenolic compound extracted from the rhizome of Curcuma longa, was found to attenuate NMDAinduced excitotoxicity in primary retinal cultures. This study was conducted to further characterize curcumin neuroprotective ability and analyze its effects on NMDA receptor (NMDAr). METHODS. NMDAr modifications were analyzed in primary retinal cell cultures using immunocytochemistry, whole-cell patch-clamp recording and western blot analysis. Cell death was evaluated with the TUNEL assay in primary retinal and hippocampal cultures. Optical fluorometric recordings with Fura 2-AM were used to monitor [Ca2+]i. RESULTS. Curcumin dose- and time-dependently protected both retinal and hippocampal neurons against NMDA-induced cell death, confirming its anti-excitotoxic property. In primary retinal cultures, in line with the observed reduction of NMDAinduced [Ca2+]i rise, whole-cell patch-clamp experiments showed that a higher percentage of retinal neurons responded to NMDA with low amplitude current after curcumin treatment. In parallel, curcumin induced an increase in NMDAr subunit type 2A (NR2A) level, with kinetics closely correlated to time-course of neuroprotection and decrease in [Ca2+]i. The relation between neuroprotection and NR2A level increase was also in line with the observation that curcumin neuroprotection required protein synthesis. Electrophysiology confirmed an increased activity of NR2A-containing NMDAr at the plasma membrane level. CONCLUSIONS. These results confirm the neuroprotective activity of curcumin against NMDA toxicity, possibly related to an increased level of NR2A, and encourage further studies for a possible therapeutic use of curcumin based on neuromodulation of NMDArs.
AB - PURPOSE. Curcumin, a phenolic compound extracted from the rhizome of Curcuma longa, was found to attenuate NMDAinduced excitotoxicity in primary retinal cultures. This study was conducted to further characterize curcumin neuroprotective ability and analyze its effects on NMDA receptor (NMDAr). METHODS. NMDAr modifications were analyzed in primary retinal cell cultures using immunocytochemistry, whole-cell patch-clamp recording and western blot analysis. Cell death was evaluated with the TUNEL assay in primary retinal and hippocampal cultures. Optical fluorometric recordings with Fura 2-AM were used to monitor [Ca2+]i. RESULTS. Curcumin dose- and time-dependently protected both retinal and hippocampal neurons against NMDA-induced cell death, confirming its anti-excitotoxic property. In primary retinal cultures, in line with the observed reduction of NMDAinduced [Ca2+]i rise, whole-cell patch-clamp experiments showed that a higher percentage of retinal neurons responded to NMDA with low amplitude current after curcumin treatment. In parallel, curcumin induced an increase in NMDAr subunit type 2A (NR2A) level, with kinetics closely correlated to time-course of neuroprotection and decrease in [Ca2+]i. The relation between neuroprotection and NR2A level increase was also in line with the observation that curcumin neuroprotection required protein synthesis. Electrophysiology confirmed an increased activity of NR2A-containing NMDAr at the plasma membrane level. CONCLUSIONS. These results confirm the neuroprotective activity of curcumin against NMDA toxicity, possibly related to an increased level of NR2A, and encourage further studies for a possible therapeutic use of curcumin based on neuromodulation of NMDArs.
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U2 - 10.1167/iovs.10-5966
DO - 10.1167/iovs.10-5966
M3 - Article
C2 - 20861489
AN - SCOPUS:79953283388
VL - 52
SP - 1070
EP - 1077
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 2
ER -