Human plasma inactive renin: purification and activation by proteases

Area of Science:

• Biochemistry
• Renal Physiology

Background:

• Inactive renin, a precursor to active renin, plays a crucial role in the renin-angiotensin-aldosterone system.
• Previous methods for purifying inactive renin were complicated by the presence of protease inhibitors, hindering activation studies.

Purpose of the Study:

• To develop a novel purification method for human plasma inactive renin.
• To investigate the protease-mediated activation of purified inactive renin and identify effective activators.

Main Methods:

• Affinity chromatography using octyl-Sepharose for hydrophobic interaction.
• Immunoaffinity chromatography with anti-human renin immunoglobulin G-Sepharose.
• Pepstatin-Sepharose chromatography to remove residual active renin.

Main Results:

• A highly purified inactive renin preparation was obtained, free from protease inhibitors.
• Human plasma kallikrein, plasmin, and cathepsin B1 effectively activated inactive renin.
• Activation occurred without significant reduction in the 56,000-dalton molecular weight and required plasma albumin.

Conclusions:

• The developed purification method allows for the study of inactive renin activation without interference from inhibitors.
• Specific proteases can activate inactive renin through mechanisms not involving substantial molecular weight reduction.
• Plasma albumin appears to be essential for the in vitro activation process.