Facilitating Mitophagy via Pink1/Parkin2 Signaling Is Essential for the Neuroprotective Effect of β-Caryophyllene against CIR-Induced Neuronal Injury

Jiangyan Rao; Yu Wu; Xiaomei Fan; Shaonan Yang; Lu Jiang; Zhi Dong; Sha Chen

doi:10.3390/brainsci12070868

Brain Sciences (Jun 2022)

Facilitating Mitophagy via Pink1/Parkin2 Signaling Is Essential for the Neuroprotective Effect of β-Caryophyllene against CIR-Induced Neuronal Injury

Jiangyan Rao,
Yu Wu,
Xiaomei Fan,
Shaonan Yang,
Lu Jiang,
Zhi Dong,
Sha Chen

Affiliations

Jiangyan Rao: The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing 400010, China
Yu Wu: The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing 400010, China
Xiaomei Fan: The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing 400010, China
Shaonan Yang: The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing 400010, China
Lu Jiang: The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing 400010, China
Zhi Dong: The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing 400010, China
Sha Chen: The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing 400010, China

DOI: https://doi.org/10.3390/brainsci12070868
Journal volume & issue: Vol. 12, no. 7
p. 868

Abstract

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Mitophagy is an important mechanism for maintaining mitochondrial homeostasis through elimination of damaged or dysfunctional mitochondria following cerebral ischemia-reperfusion (CIR) injury. β-Caryophyllene (BCP) is a natural sesquiterpene compound found in the essential oil of plants and has been shown to ameliorate CIR injury. However, whether BCP protects neurons from CIR injury by activating mitophagy is still unclear, and the underlying mechanism remains unknown. In the present study, a mouse neuron HT-22 cell of oxygen-glucose deprivation/reoxygenation (OGD/R) and C57BL/6 male mouse of transient middle artery occlusion followed by 24 h reperfusion (MCAO/R) were established the model of CIR injury. Our results show that BCP remarkably protected against cell death and apoptosis induced by OGD/R, and decreased neurologic injury, infarct volume, and the injury of neurons in CA1 region on MCAO/R mice. In addition, BCP accelerated mitophagy by regulating expression of mitochondrial autophagy marker molecules and the mt-Atp6/Rpl13 ratio (reflecting the relative number of mitochondria), and promoting autophagosome formation compared with OGD/R and MCAO/R groups both in vitro and in vivo. Furthermore, this study revealed that BCP pre-treatment could activate the Pink1/Parkin2 signaling pathway, also with mitophagy activation. To explore the mechanisms, mitochondrial division inhibitor-1 (Mdivi-1) was used to investigate the role of BCP in CIR injury. We found that Mdivi-1 not only decreased BCP-induced facilitation of mitophagy, but also significantly weakened BCP-induced protection against OGD/R and MCAO/R models, which was consistent with levels of Pink1/Parkin2 signaling pathway. Taken together, these results suggest that facilitating mitophagy via Pink1/Parkin2 signaling is essential for the neuroprotective effect of BCP against CIR injury.

Published in Brain Sciences

ISSN: 2076-3425 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.mdpi.com/journal/brainsci/

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