L-arginine enhances cell proliferation and reduces apoptosis in human endometrial RL95-2 cells

Abstract

BackgroundL-arginine is considered to be one of the most versatile amino acids due to the fact that it serves as a precursor for many important molecules in cellular physiology. When supplemented in the diet, L-arginine can increase the number of implantation sites in mice and rats, suggesting an effect at the level of the endometrium. To this end, this study determined the effect that L-arginine has on apoptosis and cell proliferation in human endometrial RL95-2 cells.ResultsL-arginine at physiological (200 micromol/L) and supra-physiological (800 micromol/L) concentrations increased cell proliferation at days 2 and 4 post-treatment with a dose-dependent effect being observed on day 2. Additionally, inhibition of nitric oxide (NO) synthase and arginase, which are responsible for the conversion of L-arginine to NO and polyamines, respectively, reduced the proliferative effect of L-arginine. L-arginine also decreased the proportion of cells with TUNEL positive nuclei and increased the ratio of cells with healthy mitochondria compared to cells with a disrupted mitochondrial membrane potential, indicating that L-arginine prevents mitochondrial mediated apoptosis in endometrial RL95-2 cells. Furthermore, exposure to L-arginine did not affect total BAD protein expression; however, L-arginine increased the abundance of phosphorylated BAD protein.ConclusionsIn summary, L-arginine added to the culture media at physiological (200 micromol/L) and supraphysiological concentrations (800 micromol/L) enhanced endometrial RL95-2 cell proliferation through mechanisms mediated by NO and polyamine biosynthesis. In addition, L-arginine reduced endometrial RL95-2 mitochondrial mediated apoptosis through increased phosphorylation of BAD protein.

Protective effect of infliximab on methotrexate-induced liver injury in rats: Unexpected drug interaction

“…The elevation of ornithine level may lead to the proliferation of cancer cells by decreasing apoptosis and cell death. [19] At the same time, cancer cells release excessive amount of NOS. Increased NO levels lead to an increase in peroxynitrite radicals, a decrease in T cell-related apoptosis and a proliferation of tumor cells.…”

HPV Type 16 Infection Switches Keratinocytes from Apoptotic to Proliferative Fate under TWEAK/Fn14 Interaction

“…The apoptotic cells were visualized by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method (Greene et al, 2013). Proliferation (apoptosis) index was equal to the number of Ki-67-positive cells (apoptotic bodies) assessed per 100 random nuclei.…”

Role of iron overload-induced macrophage apoptosis in the pathogenesis of peritoneal endometriosis

“…GnRH analogs have been proven as effective factors in the treatment of endometriosis and adenomyosis by regulating the secretion of estradiol, resulting in marked reduction in NO production and peroxynitrite formation (Kamada et al 2000). Recently, Greene et al (2013) showed the regulatory role of Larginine in NO-mediated enhancement of endometrial growth through increased BAD phosphorylation, which is accompanied by reduced apoptosis. Nevertheless, further studies are necessary to elucidate the significance of NO in the pathogenesis of endometriosis.…”