1. Annexin-A1-Derived Peptide Ac2-26 Suppresses Allergic Airway Inflammation and Remodelling in Mice
Tatiana Paula Teixeira Ferreira, et al. Cells. 2022 Feb 22;11(5):759. doi: 10.3390/cells11050759.
Annexin-A1 (AnxA1) and its N-terminal derived peptide Ac2-26 regulate the inflammatory response in several experimental models of disorders. This study evaluated the effect of endogenous AnxA1 and its N-terminal peptide Acetyl 2-26 (Ac2-26) on allergic asthma triggered by house dust mite (HDM) extract in mice. ANXA1-/- and wildtype (WT) mice were exposed to intranasal instillation of HDM every other day for 3 weeks, with analyses performed 24 h following the last exposure. Intranasal administration of peptide Ac2-26 was performed 1 h before HDM, beginning 1 week after the initial antigen application. ANXA1-/- mice stimulated with HDM showed marked exacerbations of airway hyperreactivity (AHR), eosinophil accumulation, subepithelial fibrosis, and mucus hypersecretion, all parameters correlating with overexpression of cytokines (IL-4, IL-13, TNF-α, and TGF-β) and chemokines (CCL11/eotaxin-1 and CCL2/MCP-1). Intranasal treatment with peptide Ac2-26 decreased eosinophil infiltration, peribronchiolar fibrosis, and mucus exacerbation caused by the allergen challenge. Ac2-26 also inhibited AHR and mediator production. Collectively, our findings show that the AnxA1-derived peptide Ac2-26 protects against several pathological changes associated with HDM allergic reaction, suggesting that this peptide or related AnxA1-mimetic Ac2-26 may represent promising therapeutic candidates for the treatment of allergic asthma.
2. Coadministration of kla peptide with HPRP-A1 to enhance anticancer activity
Wenjing Hao, Cuihua Hu, Yibing Huang, Yuxin Chen PLoS One. 2019 Nov 8;14(11):e0223738. doi: 10.1371/journal.pone.0223738. eCollection 2019.
The apoptosis-inducing peptide kla (KLAKLAK)2 possesses the ability to disrupt mitochondrial membranes and induce cancer cell apoptosis, but this peptide has a poor eukaryotic cell-penetrating potential. Thus, it requires the assistance of other peptides for effective translocation at micromolar concentrations. In this study, breast and lung cancer cells were treated by kla peptide co-administrated with membrane-active anticancer peptide HPRP-A1. HPRP-A1 assisted kla to enter cancer cells and localized on mitochondrial membranes to result in cytochrome C releasing and mitochondrial depolarization which ultimately induced apoptosis.The apoptosis rate was up to 65%and 45% on MCF-7 and A549 cell lines, respectively, induced by HPRP-A1 coadministration with kla group. The breast cancer model was constructed in mice, and the anticancer peptides were injected to observe the changes in cancer volume, andimmunohistochemical analysis was performed on the tissues and organs after the drug was administered. Both the weight and volume of tumor tissue were remarkable lower in HPRP-A1 with kla group compared with thosepeptidealonggroups. The results showed that the combined drug group effectively inhibited the growth of cancer and did not cause toxic damage to normal tissues, as well as exhibited significantly improvement on peptide anticancer activity in vitro and in vivo.
3. A1 Ions: Peptide-Specific and Intensity-Enhanced Fragment Ions for Accurate and Multiplexed Proteome Quantitation
Jianhui Liu, Yuan Zhou, Xinhang Hou, Chao Liu, Baofeng Zhao, Yichu Shan, Zhigang Sui, Zhen Liang, Lihua Zhang, Yukui Zhang Anal Chem. 2022 May 31;94(21):7637-7646. doi: 10.1021/acs.analchem.2c00876. Epub 2022 May 19.
Accurate proteome quantitation is of great significance to deeply understand various cellular and physiological processes. Since a1 ions, generated from dimethyl-labeled peptides, exhibited high formation efficiency (up to 99%) and enhanced intensities (2.34-fold by average) in tandem mass spectra, herein, we proposed an a1 ion-based proteome quantitation (APQ) method, which showed high quantitation accuracy (relative errors < 7%) and precision (median coefficients of variation ≤ 11%) even in a 20-fold dynamic range. Notably, due to the mass differences of a1 ions from peptides with different N-terminal amino acids, APQ demonstrated interference-free capacity by distinguishing target peptides from the coisolated ones. By designing an isobaric dimethyl labeling strategy, we achieved simultaneous proteome-wide measurements across up to eight samples. Using APQ to quantify the time-resolved proteomic profiles during a TGF-β-induced epithelial-mesenchymal transition, we found many differentially expressed proteins associated with fatty acid degradation, indicating that fatty acid metabolism reprogramming occurred during the process. The APQ method combines high quantitation accuracy with multiplexing capacity, which is suitable for deep mining and understanding of dynamic biological processes.
