Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 220, Issue -, Pages 837-851Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2022.08.095
Keywords
Diabetic nephropathy; Aldosterone; Glycation
Funding
- Symbiosis International University (SIU)
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This study discovers that the interaction between aldosterone and glycated albumin in diabetic nephropathy can cause oxidative stress, reduce levels of antioxidants and glycation detoxifying enzymes, and result in renal cell damage.
In diabetic nephropathy, hyperglycemia elevates albumin glycation and also results in increased plasma aldosterone. Both glycation and aldosterone are reported to cause oxidative stress by downregulating the NRF-2 pathway and thereby resulting in reduced levels of antioxidants and glycation detoxifying enzymes. We hypothesize that an interaction between aldosterone and glycated albumin may be responsible for amplified oxidative stress and concomitant renal cell damage. Hence, human serum albumin was glycated by methylglyoxal (MGO) in presence of aldosterone. Different structural modifications of albumin, functional modifications and aldosterone binding were analyzed. HEK-293 T cells were treated with aldosterone+glycated albumin along with inhibitors of receptors for mineralocorticoid (MR) and advanced glycation endproducts (RAGE). Cellular MGO content, antioxidant markers (nitric oxide, glutathione, catalase, superoxide dismutase, glutathione peroxidase), detoxification enzymes (aldose reductase, Glyoxalase I, II), their expression along with NRF-2 and Keap-1 were measured. Aldosterone binds to albumin with high affinity which is static and spontaneous. Cell treatment by aldosterone+glycated albumin increased intracellular MGO, MR and RAGE expression; hampered antioxidant, detoxification enzyme activities and reduced NRF-2, Keap-1 expression. Thus, the glycated albuminaldosterone interaction and its adverse effect on renal cells were confirmed. The results will help in developing better pharmacotherapeutic strategies for diabetic nephropathy.
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