Elevated plasminogen receptor expression occurs as a degradative phase event in cellular apoptosis

Area of Science:

• Cell Biology
• Biochemistry
• Molecular Biology

Background:

• Plasminogen activation (PA) is crucial for numerous extracellular proteolytic processes, including cell migration, tissue remodeling, and inflammation.
• The PA system's localization to extracellular matrices, basement membranes, fibrin, and cell surfaces underpins its diverse functions.
• Previous research indicated elevated PA during cycloheximide (CHX)-induced apoptosis in U937 cells, linked to increased plasminogen receptors (PLG-R) and urokinase plasminogen activator.

Purpose of the Study:

• To investigate the temporal relationship between increased plasminogen receptors (PLG-R) and other markers of apoptosis.
• To determine the effect of plasminogen on the rate of CHX-induced apoptosis in U937 cells.
• To elucidate the potential role of PA in the late stages of cellular apoptosis.

Main Methods:

• Flow cytometry to assess phosphatidylserine exposure and propidium iodide uptake.
• Quantification of specific plasminogen binding to U937 cells to measure PLG-R.
• Analysis of internucleosomal DNA fragmentation.
• Monitoring apoptosis rates in the presence and absence of plasminogen.

Main Results:

• The increase in PLG-R and specific plasminogen binding occurs late in apoptosis, concurrent with propidium iodide uptake and DNA fragmentation.
• This late apoptotic increase in PLG-R follows the initial rise in phosphatidylserine exposure.
• Plasminogen significantly accelerated the rate of CHX-induced apoptosis in U937 cells.

Conclusions:

• Increased plasminogen receptor expression is a late event in CHX-induced apoptosis.
• Plasminogen actively promotes and accelerates the late-stage degradative events of cellular apoptosis.
• The PA system likely plays a significant role in the execution of apoptosis.