During the process of apoptosis, the cells undergo an apoptotic body that disintegrates into a cell membrane. Now scientists have discovered that this process is controlled by a channel protein, and antibiotics can lift this control.
Apoptosis is an important normal life process. The molecular mechanism that triggers apoptosis has been extensively studied, but the regulation process of cell disintegration has not been known. The membrane membrane protein Pannexin 1 (PANX1) plays a central role in the process of disintegration of apoptotic cells. In addition, they unexpectedly found that antibiotics can inhibit the activity of PANX1. Apoptosis and antibiotics appear to be two completely unrelated areas, and PANX1 is the bridge between them.
The PANX1 channel is a complex structure that spans the cell membrane and controls the entry and exit of a large number of biologically active molecules. The most famous role of PANX1 is to control the release of ATP. Previous studies have shown that PANX1 channels open during apoptosis and release ATP. This release can induce phagocytic cells to come and swallow and digest apoptotic cells and their components. The opening of the PANX1 channel is well observed because fluorescent DNA binding dyes (such as TO-PRO-3) can enter cells via these channels.
The researchers monitored the activity of the PANX1 channel by observing the uptake of TO-PRO-3 by human apoptotic cells. They used this system to screen small-molecule libraries and found that the antibiotic trovafloxacin could be a potent inhibitor of the PANX1 channel. The researchers point out that this inhibition is not dependent on the apoptotic process.
Subsequently, the researchers used trovafloxacin to conduct an in-depth study of the PANX1 channel. They found that PANX1 channels not only regulate ATP release from apoptotic cells, but also control the formation of apoptotic bodies. Apoptotic bodies are formed when apoptotic cells are disintegrated, and are membrane structures that enclose cell debris.
When trovafloxacin inhibits the PANX1 channel, the number of apoptotic bodies is greatly increased, and the cell disintegration is abnormal. In this case, apoptotic cells produce a filamentous structure called apoptopodia that prevents the dissociation of cell membrane vesicles that occur early in apoptosis. These filamentous structures do not appear when the PANX1 channel is active.
Apoptotic bodies contain a variety of different components, such as DNA, nuclear debris, organelles, various proteins and molecules. So far, it is not clear why this structure appears. Although apoptotic bodies are quickly swallowed by phagocytic cells, phagocytic cells are also effective in swallowing intact apoptotic cells. In fact, not all apoptotic cells will disintegrate and form apoptotic bodies.
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