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Scorpion Venom Heat-Resistant Peptide Attenuates Glial Fibrillary Acidic Protein Expression via c-Jun/AP-1

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Abstract

Scorpion venom has been used in the Orient to treat central nervous system diseases for many years, and the protein/peptide toxins in Buthus martensii Karsch (BmK) venom are believed to be the effective components. Scorpion venom heat-resistant peptide (SVHRP) is an active component of the scorpion venom extracted from BmK. In a previous study, we found that SVHRP could inhibit the formation of a glial scar, which is characterized by enhanced glial fibrillary acidic protein (GFAP) expression, in the epileptic hippocampus. However, the cellular and molecular mechanisms underlying this process remain to be clarified. The results of the present study indicate that endogenous GFAP expression in primary rat astrocytes was attenuated by SVHRP. We further demonstrate that the suppression of GFAP was primarily mediated by inhibiting both c-Jun expression and its binding with AP-1 DNA binding site and other factors at the GFAP promoter. These results support that SVHRP contributes to reducing GFAP at least in part by decreasing the activity of the transcription factor AP-1. In conclusion, the effects of SVHRP on astrocytes with respect to the c-Jun/AP-1 signaling pathway in vitro provide a practical basis for studying astrocyte activation and inhibition and a scientific basis for further studies of traditional medicine.

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Fig. 1
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Abbreviations

BmK:

Buthus martensii Karsch

SVHRP:

Scorpion venom heat-resistant peptide

GFAP:

Glial fibrillary acidic protein

AP-1:

Activator protein 1

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (NSFC, 81371223 and 81371437) and the Research Fund for the Doctoral Program of Higher Education of China (20122105110010).

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Physiology, Dalian Medical University, Dalian, 116044, China

    Zhen Cao, Xue-Fei Wu, Yan Peng, Shu-Qin Zhang, Wan-Qin Zhang & Shao Li

  2. Liaoning Engineering Technology Centre of Target-Based Nature Products for Prevention and Treatment of Ageing-Related Neurodegeneration, Dalian, 116044, China

    Rui Zhang, Na Li & Jie Zhao

  3. Department of Urology, Dalian Friendship Hospital, Dalian, 116001, China

    Jin-Yi Yang

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  1. Zhen Cao
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  2. Xue-Fei Wu
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  3. Yan Peng
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  4. Rui Zhang
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  5. Na Li
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  6. Jin-Yi Yang
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  7. Shu-Qin Zhang
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  8. Wan-Qin Zhang
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  9. Jie Zhao
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  10. Shao Li
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Corresponding authors

Correspondence to Jie Zhao or Shao Li.

Electronic supplementary material

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10571_2015_215_MOESM1_ESM.tif

Supplementary material 1 (TIFF 4247 kb). Fig. S Cell morphology and survival of cultured primary astrocytes after SVHRP treatment remained unchanged. (a) Morphology of cultured primary astrocytes demonstrated by dye filling with the membrane tracer after SVHRP or vehicle treatment. (b) Live (green) and apoptotic (red) primary astrocytes stained with calcein-AM/PI after SVHRP or vehicle treatment. n = 3, scale bars are 10 μm

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Cao, Z., Wu, XF., Peng, Y. et al. Scorpion Venom Heat-Resistant Peptide Attenuates Glial Fibrillary Acidic Protein Expression via c-Jun/AP-1. Cell Mol Neurobiol 35, 1073–1079 (2015). https://doi.org/10.1007/s10571-015-0215-5

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  • DOI: https://doi.org/10.1007/s10571-015-0215-5

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