Back to Search
Start Over
Propofol inhibited autophagy through Ca2+/CaMKKβ/AMPK/mTOR pathway in OGD/R-induced neuron injury.
- Source :
-
Molecular Medicine . 11/23/2018, Vol. 24 Issue 1, pN.PAG-N.PAG. 1p. - Publication Year :
- 2018
-
Abstract
- Background: The neuroprotective role of propofol (PPF) in cerebral ischemia-reperfusion (I/R) has recently been highlighted. This study aimed to explore whether the neuroprotective mechanisms of PPF were linked to its regulation of Ca2+/CaMKKβ (calmodulin-dependent protein kinase kinase β)/AMPK (AMP-activated protein kinase)/mTOR (mammalian target of rapamycin)/autophagy pathway. Methods: Cultured primary rat cerebral cortical neurons were treated with oxygen-glucose deprivation and re-oxygenation (OGD/R) to mimic cerebral I/R injury in vitro. Results: Compared with the control neurons, OGD/R exposure successfully induced neuronal I/R injury. Furthermore, OGD/R exposure notably caused autophagy induction, reflected by augmented LC3-II/LC3-I ratio and Beclin 1 expression, decreased p62 expression, and increased LC3 puncta formation. Moreover, OGD/R exposure induced elevation of intracellular Ca2+ concentration ([Ca2+]i). However, PPF treatment significantly antagonized OGD/R-triggered cell injury, autophagy induction, and [Ca2+]i elevation. Further investigation revealed that both autophagy induction by rapamycin and [Ca2+]i elevation by the Ca2+ ionophore ionomycin significantly reversed the PPF-mediated amelioration of OGD/R-triggered cell injury. Importantly, ionomycin also significantly abrogated the PPF-mediated suppression of autophagy and CaMKKβ/AMPK/mTOR signaling in OGD/R-exposed neurons. Additionally, activation of CaMKKβ/AMPK/mTOR signaling abrogated the PPF-mediated autophagy suppression. Conclusion: Our findings demonstrate that PPF antagonized OGD/R-triggered neuronal injury, which might be mediated, at least in part, via inhibition of autophagy through Ca2+/CaMKKβ/AMPK/mTOR pathway. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10761551
- Volume :
- 24
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Molecular Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 133163761
- Full Text :
- https://doi.org/10.1186/s10020-018-0054-1