Phosphatidylserine, translocation apoptosis

The control of the processes of phosphohpid translocation and scrambling by cytoplasmic calcium concentration is known to be one factor in regulating the appearance of phosphatidylserine on the cell surface. There is now evidence that other factors are involved in modulating membrane phospholipid distribution and for preserving phospholipid homeostasis. Current research is directed to clarify the role of these agents and to establish any connections with the initiation of apoptosis. 

Changes occur at the cell surface and plasma membrane in the early stages of apoptosis. One of the major plasma membrane alterations is the translocation of phosphatidylserine (PS) from the inner side of the plasma membrane to the outer layer for external exposure (FI). This change of exposure requires the activation of caspase-3, a Ca flux over the plasma membrane, and a change in Bcl-2 family (B8,B13, M6). 

Translocation of the phosphatidylserine from the inner to the outer leaflet of the plasma membrane is an initial event related to the apoptotic process and possibly serves as a signal for the removal of apoptotic bodies by phagocytic cells (Martin et al., 1995). The exposure of this phospholipid has been largely used as a specific apoptosis marker. 

The second phase, proposed by Moghimi et al., was said to occur 24 h after exposure, and consisted of a loss of mitochondrial membrane potential which was revealed by translocation of phosphatidylserine as a consequence of PEI-induced channel formation. This led to release of the pro-apoptotic cytochrome c and subsequent activation of caspases-3 triggering apoptosis. Mitochondrial-mediated apoptotic events induced by polycations have also been reported in cell lines treated with high MW PLL in free form, DNA polyplexes and PAMAM dendrimers. In the study by Lee et al., PAMAM dendrimers around 45 nm in size exhibited mitochondrial co-localization, decreased expression of mitochondrial genes and mitochondria membrane... 

Phosphatidylserine is a membrane phospholipid, which is normally restricted to the inner leaflet of the plasma membrane. The translocation of phosphatidylserine from the inner to the outer leaflet of the plasma membrane is an early event in apoptosis. Annexin V, an endogenous human protein with a high affinity for membrane-bound phosphatidylserine, can be used in vitro to detect apoptosis. An annexin V assay in a microfluidic system has been developed for flow cytometric analysis of apoptosis using a minimal number of cells. 

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