Apoptosis in the endometrium is a key feature of the human menstrual cycle and aids in maintaining endometrial SB203580 buy homeostasis by eliminating cells from the functionalis layer during the late secretory phase. Inhibitors,Modulators,Libraries In the functionalis layer of the endometrium, apoptosis exhibits a cyclic pattern with the least amount being observed during the proliferative phase followed by an increase during the secretory phase and the maximum being observed during menstruation. The expos ure of endometrial RL95 2 cells to physiological and supraphysiological concentrations of L arginine reduced the proportion of cells that exhibited DNA fragmenta tion as assessed by TUNEL assay. Activation of endonucleases and the subsequent DNA fragmenta tion are considered to be hallmark characteristics of cells undergoing apoptosis.

To this end, the current results demonstrate that the presence of L arginine reduces the proportion Inhibitors,Modulators,Libraries of endometrial RL95 2 cells ex periencing apoptosis. Apoptosis can occur through either receptor ligand mediated pathways or mitochon drial mediated pathways, with both resulting in DNA fragmentation. Receptor ligand mediated apoptosis requires an external signal, while mitochondrial me diated apoptosis occurs through the disruption of the mitochondrial membrane. As the presence or ab sence of L arginine would represent Inhibitors,Modulators,Libraries an intracellular event rather than receptor mediated extracellular signal ing, we hypothesized that L arginines prevention of apoptosis in endometrial RL95 2 cells is mediated through the mitochondria.

The presence of L arginine in the culture media increased the ratio of cells with a healthy mitochondrial membrane compared to cells with an altered mitochondrial membrane potential. Thus, the current study indicates that L arginine reduces the incidence of endometrial RL95 2 cell Inhibitors,Modulators,Libraries apoptosis by preventing the disruption of mitochondrial membrane potential, suggesting a role for L arginine in the regula tion of endometrial epithelial apoptosis. Mitochondrial membrane potential is highly influenced by proteins that belong to the BCL2 family. The pro apoptotic protein BAX and the anti apoptotic protein BCL2 are often studied together Inhibitors,Modulators,Libraries as indicators of apoptosis. In healthy cells, a balance exists in which BCL2 is normally found imbedded in the mitochondrial membrane. Under apoptotic conditions, activated BAX will embed in the mitochondrial membrane with BCL2 and disrupt the mitochondrial membrane potential.

Accordingly, we examined if L arginines prevention of apoptosis is through a BCL2 and BAX mediated event. Interestingly, the pres ence of L arginine did not increase the ratio of BCL2 to BAX in endometrial RL95 selleck chemical 2 cells. In fact, the BCL2 to BAX mRNA and protein ratios were higher in endometrial RL95 2 cells not exposed to L arginine which were under going apoptosis through a mitochondrial mediated path way.