PINK1 Deficiency Enhances Inflammatory Cytokine Release from Acutely Prepared Brain Slices.
- Author:
Jun KIM
1
;
Ji Won BYUN
;
Insup CHOI
;
Beomsue KIM
;
Hey Kyeong JEONG
;
Ilo JOU
;
Eunhye JOE
Author Information
- Publication Type:Original Article
- Keywords: Parkinson's disease; PINK1; inflammation
- MeSH: Brain; Brain Injuries; Cytokines; Dopaminergic Neurons; Encephalitis; Hydrazines; Inflammation; Interleukin-6; Interleukins; Parkinson Disease; Phosphorylation; Phosphotransferases; Risk Factors; RNA, Messenger; Substantia Nigra; Tumor Necrosis Factor-alpha
- From:Experimental Neurobiology 2013;22(1):38-44
- CountryRepublic of Korea
- Language:English
- Abstract: Parkinson's disease (PD) is the second most common neurodegenerative motor disease caused by degeneration of dopaminergic neurons in the substantia nigra. Because brain inflammation has been considered a risk factor for PD, we analyzed whether PTEN induced putative kinase 1 (PINK1), an autosomal recessive familial PD gene, regulates brain inflammation during injury states. Using acutely prepared cortical slices to mimic injury, we analyzed expression of the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-6 at the mRNA and protein levels. Both mRNA and protein expression of these cytokines was higher at 6-24 h after slicing in PINK1 knockout (KO) slices compared to that in wild-type (WT) slices. In serial experiments to understand the signaling pathways that increase inflammatory responses in KO slices, we found that IkappaB degradation was enhanced but Akt phosphorylation decreased in KO slices compared to those in WT slices. In further experiments, an inhibitor of PI3K (LY294002) upstream of Akt increased expression of pro-inflammatory cytokines. Taken together, these results suggest that PINK1 deficiency enhance brain inflammation through reduced Akt activation and enhanced IkappaB degradation in response to brain injury.
