Chloride concentrations in human hepatic cytosol and mitochondria are a function of age

Biochemical and Biophysical Research Communications
Stephan C JahnMargaret O James

Abstract

We recently reported that, in a concentration-dependent manner, chloride protects hepatic glutathione transferase zeta 1 from inactivation by dichloroacetate, an investigational drug used in treating various acquired and congenital metabolic diseases. Despite the importance of chloride ions in normal physiology, and decades of study of chloride transport across membranes, the literature lacks information on chloride concentrations in animal tissues other than blood. In this study we measured chloride concentrations in human liver samples from male and female donors aged 1 day to 84 years (n = 97). Because glutathione transferase zeta 1 is present in cytosol and, to a lesser extent, in mitochondria, we measured chloride in these fractions by high-performance liquid chromatography analysis following conversion of the free chloride to pentafluorobenzylchloride. We found that chloride concentration decreased with age in hepatic cytosol but increased in liver mitochondria. In addition, chloride concentrations in cytosol, (105.2 ± 62.4 mM; range: 24.7-365.7 mM) were strikingly higher than those in mitochondria (4.2 ± 3.8 mM; range 0.9-22.2 mM). These results suggest a possible explanation for clinical observations seen in patients tr...Continue Reading

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Citations

Feb 7, 2016·Biochimica Et Biophysica Acta·Stephan C JahnMargaret O James
May 5, 2016·Pharmacogenomics·Margaret O James, Peter W Stacpoole
Aug 27, 2016·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Dimitrios Tsikas
Jun 2, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Guo ZhongPeter W Stacpoole
Sep 16, 2017·Journal of Clinical Pharmacology·Naveen MangalStephan Schmidt
May 1, 2020·Membranes·Jerzy J JasielecAndrzej Lewenstam
Aug 25, 2020·Analytical Chemistry·Sang-Hyun ParkInjae Shin
Sep 23, 2021·American Journal of Physiology. Cell Physiology·Harpreet Singh

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