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Curcumin exerts protective effects against hypoxia‑reoxygenation injury via the enhancement of apurinic/apyrimidinic endonuclease�1 in SH‑SY5Y cells: Involvement of the PI3K/AKT pathway
- Source :
- International Journal of Molecular Medicine
- Publication Year :
- 2020
- Publisher :
- Spandidos Publications, 2020.
-
Abstract
- Curcumin, a polyphenolic compound extracted from the plant Curcuma longa, has been reported to exert neuroprotective effects against cerebral ischemia reperfusion (I/R) injury. However, the mechanisms underlying these effects remain to be fully elucidated. Emerging evidence indicated that apurinic/apyrimidinic endonuclease 1 (APE1), a multifunctional enzyme, participates in neuronal survival against I/R injury. Therefore, the aim of the present study was to investigate whether curcumin alleviates oxygen-glucose deprivation/reper-fusion (OGD/R)-induced SH-SY5Y cell injury, which serves as an in vitro model of cerebral I/R injury, by regulating APE1. The results revealed that curcumin increased cell viability, decreased LDH activity, reduced apoptosis and caspase-3 activity, downregulated the pro-apoptotic protein Bax expression and upregulated the anti-apoptotic protein Bcl-2 expression in SH-SY5Y cells subjected to OGD/R. Simultaneously, curcumin eliminated the OGD/R-induced decreases in APE1 protein and mRNA expression, as well as 8-hydroxy-2′-deoxyguanosine (8-OHdG) level and AP sites in SH-SY5Y cells. However, APE1 knockdown by siRNA transfection markedly abrogated the protective effects of curcumin against OGD/R-induced cytotoxicity, apoptosis and oxidative stress, as illustrated by the decreases in reactive oxygen species production and NADPH oxidase 2 expression, and the increase in superoxide dismutase activity and glutathione levels in SH-SY5Y cells. Furthermore, curcumin mitigated the OGD/R-induced activation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. Treatment with LY294002, an inhibitor of PI3K/AKT pathway activity, attenuated the protective effects of curcumin on cytotoxicity and apoptosis, and reversed the curcumin-induced upregulation of APE1 protein expression in SH-SY5Y cells subjected to OGD/R. Taken together, these results demonstrated that curcumin protects SH-SY5Y cells against OGD/R injury by inhibiting apoptosis and oxidative stress, and via enhancing the APE1 level and activity, promoting PI3K/AKT pathway activation.
- Subjects :
- 0301 basic medicine
Curcumin
phosphatidylinositol 3-kinase/protein kinase B pathway
Pharmacology
medicine.disease_cause
Neuroprotection
Phosphatidylinositol 3-Kinases
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cell Line, Tumor
DNA-(Apurinic or Apyrimidinic Site) Lyase
Genetics
medicine
Humans
Protein kinase B
PI3K/AKT/mTOR pathway
chemistry.chemical_classification
Reactive oxygen species
NADPH oxidase
biology
Articles
General Medicine
Oxidative Stress
cerebral ischemia/reperfusion injury
030104 developmental biology
chemistry
Apoptosis
Reperfusion Injury
030220 oncology & carcinogenesis
biology.protein
Proto-Oncogene Proteins c-akt
apurinic/apyrimidinic endonuclease 1
Oxidative stress
Signal Transduction
Subjects
Details
- ISSN :
- 1791244X and 11073756
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Medicine
- Accession number :
- edsair.doi.dedup.....4788c4c82eb371e2d5699ab8ffd44c2c