PGC-1α-Mediated Mitochondrial Biogenesis is Involved in Cannabinoid Receptor 2 Agonist AM1241-Induced Microglial Phenotype Amelioration
Cannabinoid type 2 receptor (CB2R) agonist AM1241 induces anti-inflammation by ameliorating microglial phenotypes, the mechanism, however, is still unknown. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcription protein which can regulate mitochondrial biogenesis, and the aim of this study is to investigate whether PGC-1α is involved in AM1241-induced anti-inflammation in N9 microglial cells. We used 10 ng/ml lipopolysaccharide (LPS) plus 10 U/ml interferon γ (IFNγ) to activate microglia into classic activated phenotype (M1 phenotype), and found that co-administration of 10 µM AM1241 increased the expressions of mitochondria biogenesis-associated proteins, including nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM) and COX IV, and up-regulated the biomarker levels of microglial M2 phenotype, including arginase 1 (Arg-1) and brain-derived neurotrophic factor (BDNF), and down-regulated biomarker levels of M1 phenotype, including inducible nitric oxide synthase (iNOS) and tumor necrosis factor α (TNF-α), compared to the cells treated with LPS plus IFNγ only (P < 0.05). By using PGC-1α-siRNA, however, we found that down-regulation of PGC-1α significantly reversed the AM1241-induced effects above (P < 0.05). According to the results in this study, we found that PGC-1α may mediate CB2R agonist AM1241-induced anti-inflammation in N9 microglial cells, and the mechanism might be associated with the enhancement of mitochondria biogenesis.
KeywordsPGC-1α Cannabinoid type 2 receptor Mitochondrial biogenesis Inflammation Microglia
This work was supported by the National Natural Science Foundation of China (Grant Numbers 81601148, 81700058), and Natural Science Foundation of Shaanxi, China (Grant Number 2018JM7087).
MZ and SY designed the experiments; LM and WN performed the experiments; JL and JJ performed the analysis; SY contributed to writing. All authors have read and approved the final manuscript.
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Conflict of interest
The authors declare that they have no conflict of interest.
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