Calcium-dependent aggregation of human serum amyloid P component

Area of Science:

• Biochemistry
• Molecular Biology
• Biophysics

Background:

• Human amyloid P component (AP) is a major non-collagenous protein of amyloid deposits.
• Previous studies showed conflicting results regarding AP sedimentation behavior in density gradients.

Purpose of the Study:

• To investigate the role of calcium ions (Ca2+) in the aggregation of human amyloid P component.
• To clarify the discrepancy in reported sedimentation rates of human AP.

Main Methods:

• Ultracentrifugation of human serum and isolated human AP on density gradients.
• Varying concentrations of Ca2+ and EDTA were used in the gradients.
• Inhibition studies with serum albumin were performed.

Main Results:

• Human AP showed Ca2+-dependent aggregation at Ca2+ concentrations of 1 mM or higher.
• Aggregation was inhibited by serum albumin, indicating a requirement for free ionized Ca2+.
• AP from mouse and plaice did not exhibit similar Ca2+-dependent aggregation.

Conclusions:

• Calcium ions promote the aggregation of human amyloid P component.
• This Ca2+-dependent aggregation mechanism may be relevant to AP deposition in amyloidosis.
• The findings resolve previous discrepancies regarding human AP sedimentation behavior.