Isoflavones Inhibit Hydrogen Peroxide-Induced Angiotensinogen Secretion

TL;DR

This study shows that isoflavones like daidzein and equol can reduce hydrogen peroxide-induced angiotensinogen secretion in kidney cells, which may help prevent kidney disease.

Contribution

The study identifies isoflavones and p38 MAP kinase as inhibitors of hydrogen peroxide-induced angiotensinogen secretion in renal proximal tubular epithelial cells.

Findings

Hydrogen peroxide increases angiotensinogen secretion in renal proximal tubular epithelial cells.

Catalase, daidzein, and equol reduce angiotensinogen expression and secretion.

p38 and JNK MAP kinase pathways are involved in angiotensinogen secretion regulation.

Abstract

The renin–angiotensin system helps regulate the endocrine system in modulating blood pressure, fluid volume, and body fluid electrolyte levels. The disruption of the renin–angiotensin system can lead to kidney disease onset and progression. However, the mechanism by which kidney angiotensinogen expression and secretion induce the onset and progression of diabetic nephropathy remains unclear. In this study, we used renal proximal tubular epithelial cells, which express high levels of angiotensinogen, to examine food components that regulate angiotensinogen secretion. The renal proximal tubular epithelial cells were first treated with catalase (antioxidant), daidzein, equol (an isoflavone), a MAP kinase inhibitor, ERK, p38, or JNK and then stimulated with hydrogen peroxide. After 24 h, we collected a culture medium to perform an enzyme-linked immunosorbent assay test for angiotensinogen and cells in order to perform real-time PCR to detect angiotensinogen. We found that angiotensinogen secretion increased as the hydrogen peroxide concentration increased. Catalase, daidzein, and equol decreased angiotensinogen expression and secretion. To investigate the cell signaling mechanism involved in these effects, we assessed the contribution of the MAP kinase cascade. Our data suggest the contribution of p38 and JNK. Our study shows that, in proximal tubular epithelial cells, hydrogen peroxide stimulates angiotensinogen secretion. Isoflavones and p38 inhibited angiotensinogen secretion.

Figures