Osmotic Contribution of Synthesized Betaine by Choline Dehydrogenase Using In Vivo and In Vitro Models of Post-traumatic Syringomyelia.

IF 2.3 4区医学 Q3 BIOPHYSICS

Cellular and molecular bioengineering Pub Date : 2022-11-27 eCollection Date: 2023-02-01 DOI:10.1007/s12195-022-00749-5

Dipak D Pukale, Daria Lazarenko, Siddhartha R Aryal, Fardin Khabaz, Leah P Shriver, Nic D Leipzig

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引用次数: 0

Abstract

Introduction: Syringomyelia (SM) is a debilitating spinal cord disorder in which a cyst, or syrinx, forms in the spinal cord parenchyma due to congenital and acquired causes. Over time syrinxes expand and elongate, which leads to compressing the neural tissues and a mild to severe range of symptoms. In prior omics studies, significant upregulation of betaine and its synthesis enzyme choline dehydrogenase (CHDH) were reported during syrinx formation/expansion in SM injured spinal cords, but the role of betaine regulation in SM etiology remains unclear. Considering betaine's known osmoprotectant role in biological systems, along with antioxidant and methyl donor activities, this study aimed to better understand osmotic contributions of synthesized betaine by CHDH in response to SM injuries in the spinal cord.

Methods: A post-traumatic SM (PTSM) rat model and in vitro cellular models using rat astrocytes and HepG2 liver cells were utilized to investigate the role of betaine synthesis by CHDH. Additionally, the osmotic contributions of betaine were evaluated using a combination of experimental as well as simulation approaches.

Results: In the PTSM injured spinal cord CHDH expression was observed in cells surrounding syrinxes. We next found that rat astrocytes and HepG2 cells were capable of synthesizing betaine via CHDH under osmotic stress in vitro to maintain osmoregulation. Finally, our experimental and simulation approaches showed that betaine was capable of directly increasing meaningful osmotic pressure.

Conclusions: The findings from this study demonstrate new evidence that CHDH activity in the spinal cord provides locally synthesized betaine for osmoregulation in SM pathophysiology.

Supplementary information: The online version of this article contains supplementary material available 10.1007/s12195-022-00749-5.

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胆碱脱氢酶对创伤后脊髓空洞模型中合成甜菜碱的渗透作用

脊髓空洞症(SM)是一种使人衰弱的脊髓疾病，由于先天和后天的原因，在脊髓实质中形成囊肿或脊髓空洞。随着时间的推移，鼻腔扩张和拉长，导致神经组织受压，并出现轻微到严重的症状。在先前的组学研究中，甜菜碱及其合成酶胆碱脱氢酶(CHDH)在SM损伤脊髓中形成/扩张过程中显著上调，但甜菜碱在SM病因学中的调节作用尚不清楚。考虑到甜菜碱在生物系统中已知的渗透保护作用，以及抗氧化和甲基供体活性，本研究旨在更好地了解CHDH合成甜菜碱在脊髓SM损伤中的渗透作用。方法:采用创伤后SM大鼠模型和大鼠星形胶质细胞和HepG2肝细胞体外细胞模型，探讨CHDH对甜菜碱合成的作用。此外，甜菜碱的渗透贡献评估使用实验和模拟方法的组合。结果:创伤性脊髓创伤后，在脊髓管周围细胞中观察到CHDH的表达。我们发现大鼠星形胶质细胞和HepG2细胞在体外渗透胁迫下能够通过CHDH合成甜菜碱，维持渗透调节。最后，我们的实验和模拟方法表明甜菜碱能够直接增加有意义的渗透压。结论:本研究结果提供了新的证据，证明脊髓CHDH活性为SM病理生理中的渗透调节提供了局部合成的甜菜碱。补充信息:本文的在线版本包含补充材料:10.1007/s12195-022-00749-5。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.