Antagonism of proteasome inhibitor-induced heme oxygenase-1 expression by PINK1 mutation.

PTEN-induced putative kinase 1 (PINK1) is an integral protein in the mitochondrial membrane and maintains mitochondrial fidelity. Pathogenic mutations in PINK1 have been identified as a cause of early-onset autosomal recessive familial Parkinson's disease (PD). The ubiquitin proteasome pathway is associated with neurodegenerative diseases. In this study, we investigated whether mutations of PINK1 affects the cellular stress response following proteasome inhibition. Administration of MG132, a peptide aldehyde proteasome inhibitor, significantly increased the expression of heme oxygenase-1 (HO-1) in rat dopaminergic neurons in the substantia nigra and in the SH-SY5Y neuronal cell line. The induction of HO-1 expression by proteasome inhibition was reduced in PINK1 G309D mutant cells. MG132 increased the levels of HO-1 through the Akt, p38, and Nrf2 signaling pathways. Compared with the cells expressing WT-PINK1, the phosphorylation of Akt and p38 was lower in those cells expressing the PINK1 G309D mutant, which resulted in the inhibition of the nuclear translocation of Nrf2. Furthermore, MG132-induced neuronal death was enhanced by the PINK1 G309D mutation. In this study, we demonstrated that the G309D mutation impairs the neuroprotective function of PINK1 following proteasome inhibition, which may be related to the pathogenesis of PD.

[Distribution and pollution character of heavy metals in the surface sediments of Liao River].

The concentrations of 7 heavy metals (Ni, Cu, Cr, Pb, Cd, As, Hg) and organic matters in the surface sediments of Liao River were determined by atomic absorption spectrometry (AAS) and atomic fluorescence spectrometry (AFS), and sediments pollution assessment was carried out using geoaccumulation index. Moreover, the sources of heavy metal contamination were estimated with the principal component analysis (PCA). The results demonstrate that the heavy metal concentrations of Liao River are markedly higher than that of Liao River in 1998 and lay at medium level compared with other rivers in China. The average concentrations (mg/kg) obtained were: Ni 26.5 mg x kg(-1), Cu 37.9 mg x kg(-1), Cr 90.3 mg x kg(-1), Pb 32.9 mg x kg(-1), Cd 0.49 mg x kg(-1), As 12.3 mg x kg(-1), Hg 0.14 mg x kg(-1). The results of geoaccumulation index reveal that sediments of Liao River are uncontaminated with Ni, As, lightly contaminated with Cu, Cr, Pb and moderately contaminated with Cd, Hg. The order of the analyzed heavy metals, arranged from the highest to lowest pollution degree, is as follows Cd > Hg > Cu > Cr > Pb > As > Ni. By estimating the sources of heavy metal contamination with the Principal component analysis (PCA), it was found that the first two components account for 58.74% and 17.18% of the total variance, respectively. The industrial and living wastewater, degradation of organic matter atmospheric precipitation and geochemical changes are the main sources of heavy metal contamination.