Bee venom effects on ubiquitin proteasome system in hSOD1G85R-expressing NSC34 motor neuron cells

BMC Complementary and Alternative Medicine

Eun Jin Yang²  Sun-Mi Choi¹  MuDan Cai²  Sun Hwa Lee²  Kang-Woo Lee²  So Young Jung²  Seon Hwy Kim² 

[1] Department of Medical Research, Korea Institute of Oriental Medicine, 483 Expo-ro, Daejeon, Yuseong-gu 305-811, Republic of Korea;Department of Acupuncture & Moxibustion, Korea Institute of Oriental Medicine, 483 Expo-ro, Daejeon, Yuseong-gu 305-811, Republic of Korea

关键词: NSC34 motor neuronal cells;    Amyotrophic lateral sclerosis (ALS);    Bee venom (BV);    Ubiquitin proteasome system (UPS);    hSOD1^G85R;   

Others  :  1221067
DOI  :  10.1186/1472-6882-13-179

 received in 2013-02-12, accepted in 2013-07-11,  发布年份 2013

【 摘 要 】

Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from a progressive loss of motor neurons. Familial ALS (fALS) is caused by missense mutations in Cu, Zn-superoxide dismutase 1 (SOD1) that frequently result in the accumulation of mutant protein aggregates that are associated with impairments in the ubiquitin-proteasome system (UPS). UPS impairment has been implicated in many neurological disorders. Bee venom (BV) extracted from honey bees has been used as a traditional medicine for treating inflammatory diseases and has been shown to attenuate the neuroinflammatory events that occur in a symptomatic ALS animal model.

Methods

NSC34 cells were transiently transfected with a WT or G85R hSOD1-GFP construct for 24 hrs and then stimulated with 2.5 μg/ml BV for 24 hrs. To determine whether a SOD1 mutation affects UPS function in NSC34 cells, we examined proteasome activity and performed western blotting and immunofluorescence using specific antibodies, such as anti-misfolded SOD1, anti-ubiquitin, anti-GRP78, anti-LC3, and anti-ISG15 antibodies.

Results

We found that GFP-hSOD1^G85R overexpression induced SOD1 inclusions and reduced proteasome activity compared with the overexpression of GFP alone in NSC34 motor neuronal cells. In addition, we also observed that BV treatment restored proteasome activity and reduced the accumulation of ubiquitinated and misfolded SOD1 in GFP-hSOD1^G85R-overexpressing NSC34 motor neuronal cells. However, BV treatment did not activate the autophagic pathway in these cells.

Conclusion

Our findings suggest that BV may rescue the impairment of the UPS in ALS models.

【 授权许可】

   
2013 Kim et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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