Albumin Glycation Affects the Delivery of C-Peptide to the Red Blood Cells.
Albumin Glycation Affects the Delivery of C-Peptide to the Red Blood Cells.
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DOI：
10.1021/acsmeasuresciau.2c00001
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发表时间：
2022-06-15
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影响因子：
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通讯作者：
Spence, Dana M
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作者：
Jacobs, Monica J;Geiger, Morgan K;Summers, Suzanne E;DeLuca, Charles P;Zinn, Kurt R;Spence, Dana M
血清白蛋白是一种重要的血浆蛋白，在高血糖状态下会发生改变。在称为糖化的过程中，这些修饰可以改变蛋白质的结构和功能，从而降低配体结合能力并改变配体的生物利用度。C肽是一种与红细胞（RBC）结合并刺激三磷酸腺苷（ATP）释放的分子，已知ATP参与血液流动的调节。C肽仅在白蛋白存在时与RBC结合，并且下游信号级联仅在白蛋白和C肽复合物含有Zn 2+时发生。在这里，我们测量结合糖化牛血清白蛋白（gBSA）的RBC在有或没有C-肽和Zn 2+的条件下。这些研究的关键是分析样品的制备，包括用硼酸盐亲和色谱法分离BSA组分以及用质谱法表征不同的糖基化水平。本研究的结果显示，与具有较少糖化的样品（13%gBSA为1.22 ± 0.16 nM）相比，较高%糖化gBSA与RBC的结合增加，但递送C肽的能力降低（22%gBSA为0.75 ± 0.11 nM）。测量到Zn 2+递送至RBC的类似趋势作为糖化百分比的函数。当15%gBSA或18%gBSA与C肽/Zn 2+组合时，从RBC衍生的ATP释放分别显著增加至113%或36%。然而，26%gBSA与C-肽/Zn 2+没有显着增加ATP从RBC的释放。这些结果表明，BSA的糖化干扰C-肽和Zn 2+与RBC的结合以及随后的RBC ATP释放，这可能对1型糖尿病患者的C-肽治疗有影响。
Serum albumin is a prominent plasma protein that becomes modified in hyperglycemic conditions. In a process known as glycation, these modifications can change the structure and function of proteins, which decrease ligand binding capabilities and alter the bioavailability of ligands. C-peptide is a molecule that binds to the red blood cell (RBC) and stimulates the release of adenosine triphosphate (ATP), which is known to participate in the regulation of blood flow. C-peptide binding to the RBC only occurs in the presence of albumin, and downstream signaling cascades only occur when the albumin and C-peptide complex contains Zn2+. Here, we measure the binding of glycated bovine serum albumin (gBSA) to the RBC in conditions with or without C-peptide and Zn2+. Key to these studies is the analytical sample preparation involving separation of BSA fractions with boronate affinity chromatography and characterization of the varying glycation levels with mass spectrometry. Results from this study show an increase in binding for higher % glycation of gBSA to the RBCs, but a decrease in ability to deliver C-peptide (0.75 ± 0.11 nM for 22% gBSA) compared to samples with less glycation (1.22 ± 0.16 nM for 13% gBSA). A similar trend was measured for Zn2+ delivery to the RBC as a function of glycation percentage. When 15% gBSA or 18% gBSA was combined with C-peptide/Zn2+, the derived ATP release from the RBCs significantly increased to 113% or 36%, respectively. However, 26% gBSA with C-peptide/Zn2+ had no significant increase in ATP release from RBCs. These results indicate that glycation of BSA interferes in C-peptide and Zn2+ binding to the RBC and subsequent RBC ATP release, which may have implications in C-peptide therapy for people with type 1 diabetes.