Isolation and characterization of ZK002, a novel dual function snake venom protein from Deinagkistrodon acutus with anti-angiogenic and anti-inflammatory properties.

Autor:	Chan BD; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China., Wong WY; Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China., Lee MM; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China., Yue PY; Department of Biology, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China., Dai X; Lee's Pharmaceutical (HK) Limited, Hong Kong Science Park, Shatin, Hong Kong SAR, China., Tsim KW; Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Kowloon, Hong Kong SAR, China., Hsiao WW; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Hong Kong SAR, China., Li M; Zhaoke (Hong Kong) Ophthalmology Pharmaceutical Limited, Hong Kong Science Park, Shatin, Hong Kong SAR, China., Li XY; Zhaoke (Hong Kong) Ophthalmology Pharmaceutical Limited, Hong Kong Science Park, Shatin, Hong Kong SAR, China., Tai WC; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China.; State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute of the Hong Kong Polytechnic University, Shenzhen, Hong Kong SAR, China.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2023 Sep 29; Vol. 14, pp. 1227962. Date of Electronic Publication: 2023 Sep 29 (Print Publication: 2023).
DOI:	10.3389/fphar.2023.1227962
Abstrakt:	Introduction: Pathological angiogenesis, the abnormal or excessive generation of blood vessels, plays an important role in many diseases including cancer, diabetic retinopathy, psoriasis, and arthritis. Additionally, increasing evidence supports the close linkage between angiogenesis and inflammation. Snake venoms are a rich natural source of biologically active molecules and carry rich potential for the discovery of anti-angiogenic and anti-inflammatory modulators. Methods: Here, we isolated and purified a novel protein, ZK002, from the venom of the snake Deinagkistrodon acutus , and investigated its anti-angiogenic and anti-inflammatory activities and mechanisms. Results: ZK002 was identified as a 30 kDa heterodimeric protein of α and β chains, which exhibited anti-angiogenic activity in various in vitro assays. Mechanistically, ZK002 inhibited activation of VEGF signaling and related mediators including eNOS, p38, LIMK, and HSP27. ZK002 also upregulated the metalloproteinase inhibitor TIMP3 and inhibited components of the VEGF-induced signaling cascade, PPP3R2 and SH2D2A. The anti-angiogenic activity of ZK002 was confirmed in multiple in vivo models. ZK002 could also inhibit the in vitro expression of pro-inflammatory cytokines, as well as in vivo inflammation in the carrageenin-induced edema rat model. Conclusion: Our findings highlight the potential for further development of ZK002 as a dual function therapeutic against diseases with involvement of pathogenic angiogenesis and chronic inflammation. Competing Interests: Author XD was employed by Lee’s Pharmaceutical (HK) Limited. Authors ML and X-YL were employed by Zhaoke (Hong Kong) Ophthalmology Pharmaceutical Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Chan, Wong, Lee, Yue, Dai, Tsim, Hsiao, Li, Li and Tai.)
Databáze:	MEDLINE
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