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Structural and functional modification of THP on nitration: comparison with stone formers THP
Viswanathan Pragasam1, Periandavan Kalaiselvi, Balasubramanian Subashini
1Department of Medical Biochemistry, University of Madras, Dr. ALM PGIBMS, Taramani, Chennai, India.
Nephron. Physiology
|January 8, 2005
Summary
Oxidative damage to urinary Tamm-Horsfall glycoprotein (THP) by peroxynitrite alters its biochemical composition, promoting kidney stone formation. Nitrated THP acts as a nucleator for calcium oxalate crystals, unlike normal THP which inhibits them.
Area of Science:
- Biochemistry
- Urology
- Nephrology
Background:
- Macromolecular components in urine, particularly proteins, are crucial in the lithogenic process.
- Abnormal proteins and free radical injury are implicated in renal lithiasis pathophysiology.
- Tamm-Horsfall glycoprotein (THP) is a major urinary protein with potential roles in stone formation.
Purpose of the Study:
- To investigate the impact of the oxidant peroxynitrite on the biochemical composition of urinary THP.
- To compare the biochemical changes and crystallization behavior of nitrated THP with that of normal and stone-former THP.
Main Methods:
- THP was subjected to nitration using peroxynitrite.
- Biochemical components (thiols, S-nitrosothiol, hexose, hexosamine, sialic acid) were quantified.
- Crystallization behavior of normal, nitrated, and stone-former THP with calcium oxalate was assessed.
Main Results:
- Nitrated THP and stone-former THP showed decreased thiol, hexose, hexosamine, and sialic acid levels.
- S-nitrosothiol and NO(x) metabolites were significantly increased in nitrated and stone-former THP.
- Nitrated and stone-former THP promoted calcium oxalate nucleation and aggregation, while normal THP inhibited these processes.
Conclusions:
- Nitration of THP is a key event modifying its kinetic behavior.
- Modified THP acts as a heterogeneous nucleator in renal calculi formation.
- These findings suggest a mechanism linking oxidative stress to kidney stone pathogenesis.
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