Zaštitna uloga kurkumina u stanicama PC12 izloženim oksidacijskom stresu uzrokovanom glutamatom
| Autor: | Hua Xin Chen, Chiung Chi Peng, Chi Huang Chang, Robert Y. Peng, George Yü |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
lcsh:Biotechnology
General Chemical Engineering Glutathione reductase Excitotoxicity Pharmacology medicine.disease_cause Neuroprotection Industrial and Manufacturing Engineering chemistry.chemical_compound glutamate cytotoxicity lcsh:TP248.13-248.65 medicine nitric oxide i reactive oxidative substances curcumin PC12 cell line glutathione kurkumin apoptotični signalni put citotoksičnost glutamata stanice PC12 glutation dušikov oksid i reaktivni kisikovi spojevi chemistry.chemical_classification Reactive oxygen species Original Scientific Paper lcsh:TP368-456 Glutathione peroxidase Glutamate receptor Glutathione apoptotic pathways lcsh:Food processing and manufacture chemistry Biochemistry Oxidative stress Food Science Biotechnology |
| Zdroj: | Food Technology and Biotechnology Volume 52 Issue 4 Food Technology and Biotechnology, Vol 52, Iss 4, Pp 468-478 (2014) |
| ISSN: | 1330-9862 1334-2606 |
| Popis: | Glutamat je glavni ekscitacijski neurotransmiter u središnjem živčanom sustavu. Izmjena je glutamata i cistina (sustav xc-) glavni poveznik mehanizma obrane od oksidacijskog stresa s prijenosom živčanih podražaja i promjenom ponašanja. Prekomjerna aktivacija ionotropnih receptora glutamata dovodi do odumiranja neurona; taj se proces zove ekscitotoksičnost. Oksidacijski je stres uzrokovan glutamatom glavni uzročnik neurodegenerativnih bolesti, poput moždane ishemije, Alzheimerove i Huntingtonove bolesti. Kurkuma ima širok spektar bioloških aktivnosti, poput zaštite živčanog sustava i neurokognitivnih sposobnosti. Kurkumin smanjuje oksidacijski stres i time ublažava posljedice ishemijsko-reperfuzijske ozljede leđne moždine, epileptične napadaje i gubitak neurona u hipokampusu. Stanice PC12 feokromocitoma štakora imaju mnoge korisne osobine koje omogućuju proučavanje neurozaštitnih i neurokognitivnih aktivnosti. Ovo je istraživanje provedeno radi utvrđivanja mogućnosti praćenja aktivnost kurkumina u zaštiti živčanih stanica pomoću modela stanica PC12 oštećenih glutamatom. Rezultati pokazuju da glutamat (u koncentraciji od 20 mM) pojačava izražaj glutation peroksidaze 1, glutation disulfida, utoka iona kalcija, proizvodnju dušikovog oksida, oslobađanje citokroma c, omjer proteina Bax/Bxl-2, aktivnost kaspaze-3, oslobađanje laktat dehidrogenaze, reaktivnih kisikovih spojeva, vodikovog peroksida i malondialdehida, te smanjuje izražaj glutationa, glutation reduktaze, superoksid dismutaze i katalaze, čime se pojačava stanična apoptoza. Kurkumin ublažava sve te negativne učinke, pa se može zaključiti da učinkovito štiti stanice PC12 od oksidacijskog stresa uzrokovanog glutamatom. Njegova se aktivnost zasniva na uklanjanju reaktivnih kisikovih i dušikovih spojeva pomoću glutationa te u matriksu mitohondrija. Glutamate is a major excitatory neurotransmitter present in the central nervous system. The glutamate/cystine antiporter system xc– 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 attenuates 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 effects of curcumin can be observed via the glutamate-PC12 cell model. Results indicate that glutamate (20 mM) upregulated glutathione peroxidase 1, glutathione disulphide, Ca2+ influx, nitric oxide production, cytochrome c release, Bax/Bcl-2 ratio, caspase-3 activity, lactate dehydrogenase release, reactive oxygen species, H2O2, and malondialdehyde; and downregulated glutathione, glutathione reductase, superoxide dismutase and catalase, resulting in enhanced cell apoptosis. Curcumin alleviates all these adverse effects. Conclusively, curcumin can effectively 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|