Curcumin protects mitochondria from oxidative damage and attenuates apoptosis in cortical neurons.
OBJECTIVE
To investigate the effect of curcumin on tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in rat cortical neurons and to explore the possible mechanism.


METHODS
Primary cultured rat cortical neurons were performed in vitro and cell viability was measured by MTT assay. DNA fragmentation was used to evaluate cell apoptosis. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (Deltapsim) was determined by flow cytometric assay. Cellular glutathione (GSH) content was measured by spectrophotometer. Bcl-2 family proteins, cytochrome c, cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP) were detected by Western blot.


RESULTS
Exposure of tBHP 100 micromol/L to neurons for 60 min resulted in DYm loss and cytochrome c release from mitochondria and subsequent activation of caspase-3 and PARP cleavation, and cell apoptosis. After removal of tBHP and then further treatment with curcumin (2.5-20 micromol/L) for 18 h, curcumin abrogated Deltapsim loss and cytochrome c release, blocked activation of caspase 3, and altered the expression of Bcl-2 family. Further curcumin treatment also prevented cellular GSH and decreased intracellular ROS generation markedly. Curcumin eventually attenuated tBHP-induced apoptosis in cortical neurons.


CONCLUSIONS
Curcumin may attenuate oxidative damages in cortical neurons by reducing intracellular production of ROS and protecting mitochondria from oxidative damage.
Zhu
Yuan-gui
YG
Fujian Institute of Geriatrics, Fujian Institute of Hematology, Union Hospital, Fujian Medical University, Fuzhou 350001, China. yuangui_zhu@rush.edu
Chen
Xiao-chun
XC
Chen
Zhi-zhe
ZZ
Zeng
Yu-qi
YQ
Shi
Guang-bin
GB
Su
Yan-hua
YH
Peng
Xu
X
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D003474:Curcumin / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000037:antagonists & inhibitors
D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide; D011065:Poly(ADP-ribose) Polymerases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione; D003474:Curcumin