Lactate Production can Function to Increase Human Epithelial Cell Iron Concentration.

IF 2.3 4区 医学 Q3 BIOPHYSICS
Cellular and molecular bioengineering Pub Date : 2022-10-12 eCollection Date: 2022-12-01 DOI:10.1007/s12195-022-00741-z
Caroline Ghio, Joleen M Soukup, Lisa A Dailey, Andrew J Ghio, Dina M Schreinemachers, Ryan A Koppes, Abigail N Koppes
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Abstract

Introduction: Under conditions of limited iron availability, plants and microbes have evolved mechanisms to acquire iron. For example, metal deficiency stimulates reprogramming of carbon metabolism, increasing activity of enzymes involved in the Krebs cycle and the glycolytic pathway. Resultant carboxylates/hydroxycarboxylates then function as ligands to complex iron and facilitate solubilization and uptake, reversing the metal deficiency. Similarly, human intestinal epithelial cells may produce lactate, a hydroxycarboxylate, during absolute and functional iron deficiency to import metal to reverse limited availability.

Methods: Here we investigate (1) if lactate can increase cell metal import of epithelial cells in vitro, (2) if lactate dehydrogenase (LDH) activity in and lactate production by epithelial cells correspond to metal availability, and (3) if blood concentrations of LDH in a human cohort correlate with indices of iron homeostasis.

Results: Results show that exposures of human epithelial cells, Caco-2, to both sodium lactate and ferric ammonium citrate (FAC) increase metal import relative to FAC alone. Similarly, fumaric, isocitric, malic, and succinic acid coincubation with FAC increase iron import relative to FAC alone. Increased iron import following exposures to sodium lactate and FAC elevated both ferritin and metal associated with mitochondria. LDH did not change after exposure to deferoxamine but decreased with 24 h exposure to FAC. Lactate levels revealed decreased levels with FAC incubation. Review of the National Health and Nutrition Examination Survey demonstrated significant negative relationships between LDH concentrations and serum iron in human cohorts.

Conclusions: Therefore, we conclude that iron import in human epithelial cells can involve lactate, LDH activity can reflect the availability of this metal, and blood LDH concentrations can correlate with indices of iron homeostasis.

Abstract Image

乳酸的产生可以提高人体上皮细胞铁的浓度。
引言:在铁有效性有限的条件下,植物和微生物已经进化出获取铁的机制。例如,金属缺乏刺激碳代谢的重新编程,增加参与克雷布斯循环和糖酵解途径的酶的活性。生成的羧酸盐/羟基羧酸盐然后起到络合铁的配体的作用,促进溶解和吸收,逆转金属缺乏。类似地,在绝对和功能性缺铁期间,人类肠道上皮细胞可能会产生乳酸,一种羟基羧酸盐,以进口金属来逆转有限的可用性。方法:在这里,我们研究(1)乳酸是否可以在体外增加上皮细胞的细胞金属输入,(2)上皮细胞中的乳酸脱氢酶(LDH)活性和乳酸的产生是否对应于金属的可用性,以及(3)人类队列中的血中LDH浓度是否与铁稳态指数相关。结果:结果表明,与单独的乳酸钠和柠檬酸铁铵(FAC)相比,人类上皮细胞Caco-2暴露于乳酸钠和枸橼酸铁铵会增加金属输入。类似地,富马酸、异腈、苹果酸和琥珀酸与FAC共孵育相对于单独的FAC增加了铁的进口。暴露于乳酸钠和FAC后铁输入增加,铁蛋白和与线粒体相关的金属都升高。LDH在去铁胺暴露后没有变化,但随着FAC暴露24小时而降低。FAC培养后乳酸水平下降。对国家健康和营养检查调查的审查表明,人类队列中LDH浓度与血清铁之间存在显著的负相关关系。结论:因此,我们得出结论,人类上皮细胞中的铁输入可能涉及乳酸,LDH活性可以反映这种金属的可用性,血液LDH浓度可以与铁稳态指标相关。
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来源期刊
CiteScore
5.60
自引率
3.60%
发文量
30
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.
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