Author: Srairi-Abid, Najet ; Souid, Soumaya ; Belghazi, Maya ; Marrakchi, Naziha ; Chantome, Aurelie ; Vandier, Christophe ; Essafi-Benkhadir, Khadija ; Jebali, Jed ; Mejdoub, Hafedh ; Aissaoui-Zid, Dorra ; Ayedi, Emna ; Mlayah-Bellalouna, Saoussen

The emerging concept of small conductance Ca²⁺-activated potassium channels (SK_Ca) as pharmacological target for cancer treatment has significantly increased in recent years. In this study, we isolated the P01 toxin from Androctonus australis (Aa) scorpion venom and investigated its effect on biological properties of glioblastoma U87, breast MDA-MB231 and colon adenocarcinoma LS174 cancer cell lines. Our results showed that P01 was active only on U87 glioblastoma cells. It inhibited their proliferation, adhesion and migration with IC₅₀ values in the micromolar range. We have also shown that P01 reduced the amplitude of the currents recorded in HEK293 cells expressing SK2 channels with an IC₅₀ value of 3 pM, while it had no effect on those expressing SK3 channels. The investigation of the SK_Ca channels expression pattern showed that SK2 transcripts were expressed differently in the three cancer cell lines. Particularly, we highlighted the presence of SK2 isoforms in U87 cells, which could explain and rely on the specific activity of P01 on this cell line. These experimental data highlighted the usefulness of scorpion peptides to decipher the role of SK_Ca channels in the tumorigenesis process, and develop potential therapeutic molecules targeting glioblastoma with high selectivity.

01 Nov 2022·Brain Research Bulletin

Scorpion venom heat-resistant synthetic peptide protects dopamine neurons against 6-hydroxydopamine neurotoxicity in C. elegans

Article

Author: Chi, Xiao-Dong ; Zhao, Jie ; Yang, Jin-Yi ; Yue-Zhang ; Zhao, Wei ; Li, Shao ; Guan, Rong-Xiao ; Guo, Song-Yu ; Sui, Ao-Ran ; Supratik, Kundu

Parkinson's disease (PD) is a common neurodegenerative disease. The main pathological feature is the degeneration and loss of dopaminergic neurons in the substantia nigra, which leads to the significant decrease of dopamine content in the striatum. Our recent studies have shown that scorpion venom heat-resistant synthetic peptide (SVHRSP) have protective effects on neuroinflammation. In this study, using C. elegans induced by 6-hydroxydopamine (6-OHDA) as neurodegenerative model, we investigated the effect of SVHRSP on dopaminergic neurons neurotoxicity. Our results implied that SVHRSP treatment could improve the motor capacity in 6-OHDA-induced C. elegans and improve dopaminergic neuron mediated food sensitivity behavior. After SVHRSP treatment, dopaminergic neuron degeneration induced by 6-OHDA was significantly prevented along with a decreased α-synuclein aggregation and restored lipid deposition in C. elegans induced by 6-OHDA. We also observed the reduced levels of reactive oxygen species (ROS) after SVHRSP treatment in model-building C. elegans. In addition, the genes related to apoptosis, oxidative stress, like ctl-1, egl-1and cat-2 in C. elegans induced by 6-OHDA upregulated after treatment with SVHRSP. In conclusion, SVHRSP may impose anti-PD effect through its neuroprotective action on dopaminergic neurons. This study elucidates the effect and related mechanism of SVHRSP on PD and provides evidences for the therapeutic treatment of PD.

03 Oct 2022·Mediators of Inflammation

Proteomic Analysis of Exudates from Chronic Ulcer of Diabetic Foot Treated with Scorpion Antimicrobial Peptide

Article

Author: Yu, Zhiguo ; Meng, Lanxia ; Wu, Yingliang ; Tan, Zhixiang ; Xu, Xiaobo ; Yu, Mosheng ; Zhu, Zhanyong ; Tao, Rui

Scorpion peptides have good therapeutic effect on chronic ulcer of diabetic foot, but the related pharmacological mechanism has remained unclear. The different proteins and bacteria present in ulcer exudates from chronic diabetic foot patients, treated with scorpion antimicrobial peptide at different stages, were analyzed using isobaric tags for quantification-labeled proteomics and bacteriological methods. According to the mass spectrometry data, a total of 1865 proteins were identified qualitatively, and the number of the different proteins was 130 (mid/early), 401 (late/early), and 310 (mid, late/early). In addition, functional annotation, cluster analysis of effects and the analysis of signal pathway, transcription regulation, and protein-protein interaction network were carried out. The results showed that the biochemical changes of wound microenvironment during the treatment involved activated biological functions such as protein synthesis, cell proliferation, differentiation, migration, movement, and survival. Inhibited biological functions such as cell death, inflammatory response, immune diseases, and bacterial growth were also involved. Bacteriological analysis showed that Burkholderia cepacia was the main bacteria in the early and middle stage of ulcer exudate and Staphylococcus epidermidis in the late stage. This study provides basic data for further elucidation of the molecular mechanism of diabetic foot.

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