{"title":"羟乙基淀粉130/0.4引起的载脂蛋白A-I结构变化揭示潜在的毒性机制","authors":"Lingyan Qu, Liqun Jia, Jianzhong Zhang, Shuqin Ni","doi":"10.1007/s10930-025-10283-8","DOIUrl":null,"url":null,"abstract":"<div><p>6% hydroxyethyl starch (HES 130/0.4) is frequently employed to address hypovolemia, ensuring sufficient organ perfusion and oxygen transport. The effects on Apolipoprotein A-I (ApoA-I) were examined at three temperatures—280, 295, and 310 K—through several spectroscopic techniques to explore its possible interaction with the predominant protein in veins. The experimental findings indicated that HES 130/0.4 efficiently extinguished the intrinsic fluorescence of APOA-I. We also assessed the binding sites, binding constant, and thermodynamic parameters, which indicated that HES 130/0.4 can spontaneously associate with APOA-I via hydrogen bonds and van der Waals interactions (Δ<i>G</i> = − 1.93 × 10<sup>4</sup> J·mol<sup>−1</sup>, Δ<i>H</i> = − 5.63 × 10<sup>4</sup> J mol⁻<sup>1</sup>, and Δ<i>S</i> = − 119 J mol⁻<sup>1</sup> K⁻<sup>1</sup>) with a single binding site and week binding forces (<i>n</i> = 1.03 and <i>K</i><sub><i>A</i></sub> = 1.78 × 10<sup>3</sup> M<sup>−1</sup>) at body temperature. Moreover, the structure of APOA-I was significantly altered in the presence of HES 130/0.4. Blood Ca<sup>2+</sup> and Fe<sup>3+</sup> will diminish the storage duration. The study provides accurate and thorough foundational data to clarify the binding mechanisms of HES 130/0.4 with APOA-I in vitro, which may help the comprehension of its impact on protein function and toxic mechanism during transit and distribution in the bloodstream.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"44 5","pages":"667 - 674"},"PeriodicalIF":1.4000,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Structural Changes of Apolipoprotein A-I Caused by Hydroxyethyl Starch 130/0.4 Reveals Potential Toxic Mechanisms\",\"authors\":\"Lingyan Qu, Liqun Jia, Jianzhong Zhang, Shuqin Ni\",\"doi\":\"10.1007/s10930-025-10283-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>6% hydroxyethyl starch (HES 130/0.4) is frequently employed to address hypovolemia, ensuring sufficient organ perfusion and oxygen transport. The effects on Apolipoprotein A-I (ApoA-I) were examined at three temperatures—280, 295, and 310 K—through several spectroscopic techniques to explore its possible interaction with the predominant protein in veins. The experimental findings indicated that HES 130/0.4 efficiently extinguished the intrinsic fluorescence of APOA-I. We also assessed the binding sites, binding constant, and thermodynamic parameters, which indicated that HES 130/0.4 can spontaneously associate with APOA-I via hydrogen bonds and van der Waals interactions (Δ<i>G</i> = − 1.93 × 10<sup>4</sup> J·mol<sup>−1</sup>, Δ<i>H</i> = − 5.63 × 10<sup>4</sup> J mol⁻<sup>1</sup>, and Δ<i>S</i> = − 119 J mol⁻<sup>1</sup> K⁻<sup>1</sup>) with a single binding site and week binding forces (<i>n</i> = 1.03 and <i>K</i><sub><i>A</i></sub> = 1.78 × 10<sup>3</sup> M<sup>−1</sup>) at body temperature. Moreover, the structure of APOA-I was significantly altered in the presence of HES 130/0.4. Blood Ca<sup>2+</sup> and Fe<sup>3+</sup> will diminish the storage duration. The study provides accurate and thorough foundational data to clarify the binding mechanisms of HES 130/0.4 with APOA-I in vitro, which may help the comprehension of its impact on protein function and toxic mechanism during transit and distribution in the bloodstream.</p></div>\",\"PeriodicalId\":793,\"journal\":{\"name\":\"The Protein Journal\",\"volume\":\"44 5\",\"pages\":\"667 - 674\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2025-08-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Protein Journal\",\"FirstCategoryId\":\"2\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s10930-025-10283-8\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Protein Journal","FirstCategoryId":"2","ListUrlMain":"https://link.springer.com/article/10.1007/s10930-025-10283-8","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Structural Changes of Apolipoprotein A-I Caused by Hydroxyethyl Starch 130/0.4 Reveals Potential Toxic Mechanisms
6% hydroxyethyl starch (HES 130/0.4) is frequently employed to address hypovolemia, ensuring sufficient organ perfusion and oxygen transport. The effects on Apolipoprotein A-I (ApoA-I) were examined at three temperatures—280, 295, and 310 K—through several spectroscopic techniques to explore its possible interaction with the predominant protein in veins. The experimental findings indicated that HES 130/0.4 efficiently extinguished the intrinsic fluorescence of APOA-I. We also assessed the binding sites, binding constant, and thermodynamic parameters, which indicated that HES 130/0.4 can spontaneously associate with APOA-I via hydrogen bonds and van der Waals interactions (ΔG = − 1.93 × 104 J·mol−1, ΔH = − 5.63 × 104 J mol⁻1, and ΔS = − 119 J mol⁻1 K⁻1) with a single binding site and week binding forces (n = 1.03 and KA = 1.78 × 103 M−1) at body temperature. Moreover, the structure of APOA-I was significantly altered in the presence of HES 130/0.4. Blood Ca2+ and Fe3+ will diminish the storage duration. The study provides accurate and thorough foundational data to clarify the binding mechanisms of HES 130/0.4 with APOA-I in vitro, which may help the comprehension of its impact on protein function and toxic mechanism during transit and distribution in the bloodstream.
期刊介绍:
The Protein Journal (formerly the Journal of Protein Chemistry) publishes original research work on all aspects of proteins and peptides. These include studies concerned with covalent or three-dimensional structure determination (X-ray, NMR, cryoEM, EPR/ESR, optical methods, etc.), computational aspects of protein structure and function, protein folding and misfolding, assembly, genetics, evolution, proteomics, molecular biology, protein engineering, protein nanotechnology, protein purification and analysis and peptide synthesis, as well as the elucidation and interpretation of the molecular bases of biological activities of proteins and peptides. We accept original research papers, reviews, mini-reviews, hypotheses, opinion papers, and letters to the editor.