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Proteasome as a Molecular Target of Microcystin-LR.

Zhu Z, Zhang L, Shi G - Toxins (Basel) (2015)

Bottom Line: MC-LR at 1 nM can inhibit up to 54% of the purified 20S proteasome TL activity and 43% of the proteasome TL activity in the liver of the cyprinid rare minnow (Gobiocypris rarus).Protein degradation was retarded in GFP-CL1-transfected PC-3 cells because MC-LR inhibited the proteasome TL activity.Docking studies indicated that MC-LR blocked the active site of the proteasome β2 subunit; thus, the proteasome TL activity was inhibited.

View Article: PubMed Central - PubMed

Affiliation: School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China. zhuzhu@ustb.edu.cn.

ABSTRACT
Proteasome degrades proteins in eukaryotic cells. As such, the proteasome is crucial in cell cycle and function. This study proved that microcystin-LR (MC-LR), which is a toxic by-product of algal bloom, can target cellular proteasome and selectively inhibit proteasome trypsin-like (TL) activity. MC-LR at 1 nM can inhibit up to 54% of the purified 20S proteasome TL activity and 43% of the proteasome TL activity in the liver of the cyprinid rare minnow (Gobiocypris rarus). Protein degradation was retarded in GFP-CL1-transfected PC-3 cells because MC-LR inhibited the proteasome TL activity. Docking studies indicated that MC-LR blocked the active site of the proteasome β2 subunit; thus, the proteasome TL activity was inhibited. In conclusion, MC-LR can target proteasome, selectively inhibit proteasome TL activity, and retard protein degradation. This study may be used as a reference of future research on the toxic mechanism of MC-LR.

No MeSH data available.


Related in: MedlinePlus

MC-LR inhibits the proteasome TL activity in the liver of G. rarus. (n = 5, significances vs. the control: *p < 0.05, **p < 0.01)
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toxins-07-02221-f003: MC-LR inhibits the proteasome TL activity in the liver of G. rarus. (n = 5, significances vs. the control: *p < 0.05, **p < 0.01)

Mentions: G. rarus is an emerging fish model in aquatic toxicology in China [34]. This species is sensitive to environmental endocrine disruptors [35]. In our study, G. rarus individuals were exposed to different MC-LR concentrations for two days to verify whether MC-LR inhibits the proteasome TL activity in vivo. The proteasome TL activity in the liver of G. rarus was subsequently determined. The proteasome TL activity in the liver of G. rarus was dose-dependently inhibited by MC-LR (Figure 3). Moreover, 1 nM MC-LR resulted in a 43% inhibition rate. These data indicated that MC-LR could inhibit proteasome TL activity in vivo.


Proteasome as a Molecular Target of Microcystin-LR.

Zhu Z, Zhang L, Shi G - Toxins (Basel) (2015)

MC-LR inhibits the proteasome TL activity in the liver of G. rarus. (n = 5, significances vs. the control: *p < 0.05, **p < 0.01)
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488699&req=5

toxins-07-02221-f003: MC-LR inhibits the proteasome TL activity in the liver of G. rarus. (n = 5, significances vs. the control: *p < 0.05, **p < 0.01)
Mentions: G. rarus is an emerging fish model in aquatic toxicology in China [34]. This species is sensitive to environmental endocrine disruptors [35]. In our study, G. rarus individuals were exposed to different MC-LR concentrations for two days to verify whether MC-LR inhibits the proteasome TL activity in vivo. The proteasome TL activity in the liver of G. rarus was subsequently determined. The proteasome TL activity in the liver of G. rarus was dose-dependently inhibited by MC-LR (Figure 3). Moreover, 1 nM MC-LR resulted in a 43% inhibition rate. These data indicated that MC-LR could inhibit proteasome TL activity in vivo.

Bottom Line: MC-LR at 1 nM can inhibit up to 54% of the purified 20S proteasome TL activity and 43% of the proteasome TL activity in the liver of the cyprinid rare minnow (Gobiocypris rarus).Protein degradation was retarded in GFP-CL1-transfected PC-3 cells because MC-LR inhibited the proteasome TL activity.Docking studies indicated that MC-LR blocked the active site of the proteasome β2 subunit; thus, the proteasome TL activity was inhibited.

View Article: PubMed Central - PubMed

Affiliation: School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China. zhuzhu@ustb.edu.cn.

ABSTRACT
Proteasome degrades proteins in eukaryotic cells. As such, the proteasome is crucial in cell cycle and function. This study proved that microcystin-LR (MC-LR), which is a toxic by-product of algal bloom, can target cellular proteasome and selectively inhibit proteasome trypsin-like (TL) activity. MC-LR at 1 nM can inhibit up to 54% of the purified 20S proteasome TL activity and 43% of the proteasome TL activity in the liver of the cyprinid rare minnow (Gobiocypris rarus). Protein degradation was retarded in GFP-CL1-transfected PC-3 cells because MC-LR inhibited the proteasome TL activity. Docking studies indicated that MC-LR blocked the active site of the proteasome β2 subunit; thus, the proteasome TL activity was inhibited. In conclusion, MC-LR can target proteasome, selectively inhibit proteasome TL activity, and retard protein degradation. This study may be used as a reference of future research on the toxic mechanism of MC-LR.

No MeSH data available.


Related in: MedlinePlus