Inhibition of Kidney Mitochondrial Monoamine Oxidase Activity by the Nephrosis-Producing Aminonucleoside of Puromycin

Authors

Paul Bartlett
Mei-hwa Tu
Kathleen Ashworth

Abstract

Intraperitoneal administration in rats of a single large injection of the potent nephrotogenic aminonucleoside,6-dimethylamino-9-(3'-amino-3' =deoxy-β-D-ribofuranosyl)-purine, resulted in striking reductions in kidney cortex mitochondrial monoamine oxidase (MAO) activity, assayed on tyramine substrate The alterations in enzymatic activity correlated remarkably well with the onset and development of the massive proteinuria characteristic of the disease. The inhibitory effects were also produced in vitro, and Lineweaver-Burk reciprocal plots were clearly indicative of non-competitive inhibition. It is suggested that aminonucleoside inhibition of kidney mitochondrial MAO activity may be a biochemical lesion in the primary step of GBM collagen cross-link formation, whereby collagen fibrillogenesis is impaired and semipermeability of the GBM to macromolecular plasma proteins altered. Observation of relatively high concentrations of 5-hydroxytryptamine in aminonucleoside-nephrotic rat kidneys suggests significant impairment of serotonin, and probably also catecholamine, metabolism in the diseased kidneys.

Recommended Citation

Bartlett, Paul; Tu, Mei-hwa; and Ashworth, Kathleen (1972) "Inhibition of Kidney Mitochondrial Monoamine Oxidase Activity by the Nephrosis-Producing Aminonucleoside of Puromycin," Henry Ford Hospital Medical Journal : Vol. 20 : No. 3 , 145-152.
Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol20/iss3/4