Curcumin-Protected PC12 Cells Against Glutamate-Induced Oxidative Toxicity

Abstract

SummaryGlutamate is a major excitatory neurotransmi er present in the central nervous system. The glutamate/cystine antiporter system x c -connects the antioxidant defense with neurotransmission and behaviour. Overactivation of ionotropic glutamate receptors induces neuronal death, a pathway called excitotoxicity. Glutamate-induced oxidative stress is a major contributor to neurodegenerative diseases including cerebral ischemia, Alzheimer's and Huntington's disease. Curcuma has a wide spectrum of biological activities regarding neuroprotection and neurocognition. By reducing the oxidative damage, curcumin a enuates a spinal cord ischemia-reperfusion injury, seizures and hippocampal neuronal loss. The rat pheochromocytoma (PC12) cell line exhibits many characteristics useful for the study of the neuroprotection and neurocognition. This investigation was carried out to determine whether the neuroprotective eff ects of curcumin can be observed via the glutamate-PC12 cell model. Results indicate that glutamate (20 mM) upregulated glutathione peroxidase 1, glutathione disulphide, Ca 2+ infl ux, nitric oxide production, cytochrome c release, Bax/Bcl-2 ratio, caspase-3 activity, lactate dehydrogenase release, reactive oxygen species, H 2 O 2 , and malondialdehyde; and downregulated glutathione, glutathione reductase, superoxide dismutase and catalase, resulting in enhanced cell apoptosis. Curcumin alleviates all these adverse eff ects. Conclusively, curcumin can eff ectively protect PC12 cells against the glutamate-induced oxidative toxicity. Its mode of action involves two pathways: the glutathione-dependent nitric oxide-reactive oxygen species pathway and the mitochondria-dependent nitric oxide-reactive oxygen species pathway.

Curcuminoids combined with gefitinib mediated apoptosis and autophagy of human oral cancer SAS cells in vitro and reduced tumor of SAS cell xenograft mice in vivo

“…We also used flow cytometric assay to show that gefitinib co‐treated with CUR, DMC, or BDMC reduced MMP and increased caspase‐ 3 activities in SAS cells. It is well known that some of anticancer drugs induced cell apoptosis through mitochondria‐dependent pathways and caspase‐dependent and ‐independent pathways . Based on these observations, we suggest that gefitinib combined with CUR, DMC, or BDMC for inducing cell apoptosis of SAS cells through mitochondria‐ and caspase‐dependent pathway.…”

Astaxanthin Protects PC12 Cells against Homocysteine- and Glutamate-Induced Neurotoxicity

“…The cell viability test with MTT assay was carried out as previous reported [14]. The doses of Glu and Hcy were applied as indicated.…”

“…Hcy acts as an agonist at the glutamate binding site of the N-methyl-D-aspartate receptor [11]. The PC12 cell line, originally isolated from a pheochromocytoma in the rat adrenal medulla, has become an in vitro model for studying numerous problems in neurobiology, neurochemistry [12,13], and Alzheimer's and Parkinson's diseases [14]. Like glutamate, Hcy induced calcium influx, depolarization of mitochondrial membrane potential, and changes of Bcl-2 and Bcl-xL in the PC12 cell model [15].…”

Protective Effects of Curcumin against Formaldehyde-induced Renal Toxicity in Rats

“…In our study, rats in the formaldehyde group had increased renal NO, while a lower NO level was found in formaldehyde+curcumin group, as compared to formaldehyde alone. Many studies showed that curcumin was able to decrease the NO synthase production in activated macrophages (37) and prevented the production of NO (38,39). Curcumin prevents the formation of peroxynitrite by its radical scavenging activity and also suppresses the NO synthesis through the inhibition of iNOS activity.…”