Suppressing Cdk5 Activity by Luteolin Inhibits MPP+-Induced Apoptotic of Neuroblastoma through Erk/Drp1 and Fak/Akt/GSK3β Pathways
| Autor: | Pennapa Chonpathompikunlert, Pilaiwanwadee Hutamekalin, Ratchaneekorn Reudhabibadh, Thunwa Binlateh, Pithi Chanvorachote, Nongyao Nonpanya, Peerada Prommeenate |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
MAPK/ERK pathway
Dynamins 1-Methyl-4-phenylpyridinium Cdk5 Pharmaceutical Science medicine.disease_cause Neuroprotection Article Analytical Chemistry lcsh:QD241-441 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine lcsh:Organic chemistry Drug Discovery medicine Humans oxidative stress Viability assay Physical and Theoretical Chemistry Phosphorylation luteolin Extracellular Signal-Regulated MAP Kinases Protein kinase B 030304 developmental biology 0303 health sciences Glycogen Synthase Kinase 3 beta Dopaminergic Neurons Organic Chemistry Neurotoxicity apoptosis Cyclin-Dependent Kinase 5 Parkinson Disease medicine.disease 1-methyl-4-phenylpyridinium ion Cell biology Neuroprotective Agents chemistry Chemistry (miscellaneous) Focal Adhesion Protein-Tyrosine Kinases Mitochondrial Membranes Parkinson’s disease Molecular Medicine Luteolin Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery Oxidative stress Signal Transduction |
| Zdroj: | Molecules Volume 26 Issue 5 Molecules, Vol 26, Iss 1307, p 1307 (2021) |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules26051307 |
| Popis: | Parkinson’s disease (PD) is characterized by the progressive degeneration of dopaminergic neurons. The cause of PD is still unclear. Oxidative stress and mitochondrial dysfunction have been linked to the development of PD. Luteolin, a non-toxic flavonoid, has become interested in an alternative medicine, according to its effects on anti-oxidative stress and anti-apoptosis, although the underlying mechanism of luteolin on PD has not been fully elucidated. This study aims to investigate whether luteolin prevents neurotoxicity induction by 1-methyl-4-phenylpyridinium iodide (MPP+), a neurotoxin in neuroblastoma SH-SY5Y cells. The results reveal that luteolin significantly improved cell viability and reduced apoptosis in MPP+-treated cells. Increasing lipid peroxidation and superoxide anion (O2ˉ), including mitochondrial membrane potential (Δψm) disruption, is ameliorated by luteolin treatment. In addition, luteolin attenuated MPP+-induced neurite damage via GAP43 and synapsin-1. Furthermore, Cdk5 is found to be overactivated and correlated with elevation of cleaved caspase-3 activity in MPP+-exposed cells, while phosphorylation of Erk1/2, Drp1, Fak, Akt and GSK3β are inhibited. In contrast, luteolin attenuated Cdk5 overactivation and supported phosphorylated level of Erk1/2, Drp1, Fak, Akt and GSK3β with reducing in cleaved caspase-3 activity. Results indicate that luteolin exerts neuroprotective effects via Cdk5-mediated Erk1/2/Drp1 and Fak/Akt/GSK3β pathways, possibly representing a potential preventive agent for neuronal disorder. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|