Subcellular localization of exogenously administered renin in mouse kidney

Area of Science:

• Nephrology
• Biochemistry
• Cell Biology

Background:

• Renin is a key enzyme in the renin-angiotensin system, regulating blood pressure.
• Understanding exogenous renin's fate in the kidney is crucial for its therapeutic applications.

Purpose of the Study:

• To determine the subcellular localization of exogenously administered 125I-labeled mouse submaxillary renin in mouse kidneys.
• To investigate the uptake and distribution mechanisms of exogenous renin within renal cells.

Main Methods:

• Intravenous administration of 125I-labeled mouse submaxillary renin to ICR mice.
• Subcellular fractionation using differential and sucrose density gradient centrifugation.
• Identification of renin via specific antiserum and molecular weight determination.
• Light and electron microscopic autoradiography for cellular localization.

Main Results:

• 125I-labeled renin was primarily found in the heavy mitochondrial fraction.
• Radioactivity peaked at 1.2 M and 1.5 M sucrose densities.
• Over 90% of radioactivity was intact 125I-labeled renin (38,000 daltons).
• Autoradiography showed renin accumulation in the apical region of proximal convoluted tubular cells, specifically within lysosomal granules.

Conclusions:

• Exogenous renin filtered through glomerular capillaries is reabsorbed by proximal convoluted tubular cells.
• The primary localization of exogenous renin is within the lysosomes of these renal cells.
• This finding provides insight into the renal handling and potential intracellular fate of administered renin.