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Oxalate binding proteins in calcium oxalate nephrolithiasis
Ramasamy Selvam1, Periandavan Kalaiselvi
1Department of Medical Biochemistry, Dr ALM Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.
Urological Research
|July 12, 2003
Summary
Kidney oxalate binding proteins, found in mitochondria and nucleus, bind oxalate and influence calcium oxalate crystal formation. Their activity increases with lipid peroxidation and decreases with reduced thiol status in hyperoxaluric conditions.
Area of Science:
- Biochemistry
- Nephrology
- Molecular Biology
Background:
- Oxalate-specific binding proteins exist in human and rat kidney cells, localized in subcellular organelles like mitochondria and the nucleus.
- These proteins play a role in cellular oxalate handling and potentially in the formation of kidney stones.
Purpose of the Study:
- To characterize the oxalate binding proteins in human and rat kidneys.
- To investigate the kinetic properties and behavior of these proteins under normal and hyperoxaluric conditions, including their role in calcium oxalate crystal formation.
Main Methods:
- Isolation and purification of oxalate binding proteins from kidney subcellular organelles (mitochondria, nucleus).
- Characterization of protein composition, kinetic properties (specificity, saturability, pH/temperature dependency, inhibition), and sensitivity to transport inhibitors (DIDS).
- Assessment of oxalate binding activity in experimental hyperoxaluric models (in vitro and in vivo) and evaluation of their effect on calcium oxalate crystal nucleation and aggregation.
Main Results:
- Purified mitochondrial and nuclear oxalate binding proteins, along with a 45 kDa calcium oxalate binding protein, were identified and characterized.
- All identified oxalate binding proteins exhibited specific, saturable, and energy-dependent binding kinetics, sensitive to DIDS.
- In hyperoxaluric conditions, renal oxalate binding proteins showed enhanced activity correlated with increased lipid peroxidation and decreased thiol status. These proteins modulated calcium oxalate crystal growth, with peroxidation altering their promoting or inhibiting effects.
Conclusions:
- Renal oxalate binding proteins are key players in cellular oxalate metabolism and calcium oxalate crystal formation.
- Their activity is influenced by oxidative stress (lipid peroxidation and thiol status), suggesting a role in the pathogenesis of kidney stones.
- These proteins may modulate kidney stone crystallization processes, similar to calcium-specific binding protein modulators.