MECP2 promotes cell proliferation by activating ERK1/2 and inhibiting p38 activity in human hepatocellular carcinoma HEPG2 cells.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and currently represents the leading cause of death amongst cirrhotic patients, but the mechanisms remain unknown. In this experiment, we investigated the expression of Methyl CpG-binding protein 2 (MeCP2) in HCC, the effect of MeCP2 on the proliferation of human HCC HepG2 cells, and the activation of mitogen-activated protein kinases (MAPKs) signaling pathways. The results showed that MeCP2 expression levels was higher in human HCC tissue than normal hepatocellular tissue, and MeCP2 siRNA reduced the proliferation of HCC HepG2 cells by decreasing cell activity and cell division in vitro. After MeCP2 siRNA treatment, the proportion of G1/G0 phase cells increased, but the proportion of S and G2/M phase cells decreased, indicative of G1/G0 cell cycle arrest. Furthermore, the proportions of early and late apoptosis in HCC HepG2 cells were enhanced after MeCP2 siRNA treatment. It was also found that activation of extracellular signal-regulated protein kinase (ERK) and p38 signaling pathways were involved in the proliferation of HepG2 cells. After MeCP2 siRNA treatment, p-ERK1/2 levels decreased, but p-p38 levels increased. Our findings demonstrated that MeCP2 promoted the proliferation of human HCC HepG2 cells with activation of ERK1/2 signaling pathways, suggesting a novel mechanism for pharmacological study of treatment for human HCC.

The decreased self-renewal potential of NPCs during human embryonic brain development with reduced activity of MAPKs.

Study of neural progenitor cells (NPCs) is important for treatment of degerative diseases in central nervous system. One of the key questions in NPCs transplantation therapy is about the understanding of which stage of the NPCs in brain development is ideal. Herein we investigated survival, proliferation and apoptosis of NPCs from 12 w, 16 w and 20 w human embryonic brain, meanwhile, the phosphorylation of mitogen-activated protein kinases (MAPKs) signaling were analyzed. The results showed that the survival, proliferation and cell division of 16 w and 20 w human NPCs significantly decreased comparing with 12 w human NPCs in vitro; and the NPCs apoptosis remarkably increased. Phosphorylation of ERK1/2 of 16 w and 20 w NPCs significantly decreased comparing with 12 w human NPCs, however phosphorylation of p38 MAPK increased. NPCs proliferation increase when ERK1/2 signaling is activated by PMA. The results demonstrated that self-renewal potential of NPCs decreased in culture during human embryonic brain development, the activity of ERK signaling pathway were decreased, and suggest NPCs from 12-week fetuses might be better donor for cell transplantation during the period of 12-20 weeks because of their advantage on survival and proliferation.

STAT1/2 is involved in the inhibition of cell growth induced by U0126 in HeLa cells.

The mitogen-activated protein kinase (MAPK) signaling cascade plays an important role in cell life. Herein we show that small interfering RNAs targeting MAPK1 can inhibit HeLa cell growth and induce apoptosis along with up-regulation of signal transducers and activator 1 and 2 (STAT1/2). However, across-talk between the ras-raf-ERK1/2 signalling cascade and the JAK-STAT pathway remain largely unknown. Using MEK inhibitor U0126 and JAK-2 inhibitor AG490, we analyzed the relationship between ERK1/2 and STAT1/2 in HeLa cells. U0126 inhibited HeLa cell growth, arrested the cell cycle at G1/G0, and induced cell apoptosis, and AG490 partially reversed the effects of U0126. U0126 induced up-regulation of ERK1/2 and down-regulation of phosphorylated ERK1/2, increased STAT1 and STAT2 expression in a dose-dependent manner, and activated STAT1/2 via their phosphorylation. AG490 markedly inhibited the phosphorylation of STAT1 and STAT2 and slightly increased that of ERK1/2 inhibited by U0126. We suggest that STAT1/2 is involved in the inhibition of cell growth induced by U0126 in HeLa cells.

Asymptomatic normotensive primary aldosteronism. Case report.

We report a case of primary aldosteronism in a 30-year-old woman without hypertension or any other characteristic symptoms. The condition was first suspected by hypokalemia (2.6 mEq/liter), which was incidentally found by routine checkup. There was evidence of suppressed plasma renin activity (PRA) and elevated plasma aldosterone levels. However, the blood pressure never reached a hypertensive level, and the circulating blood volume was within a normal range. A functioning right adrenal tumor was diagnosed by adrenal scintigraphy, computerized x-ray tomography, and adrenal venography. Adrenal venous catheterization suggested an aldosteronoma, which was confirmed by lateralized hypersecretion of aldosterone. After removal of the benign adenoma, the biochemical abnormalities were corrected, yet the blood pressure remained much the same. Hypertension is not necessarily a sign of primary aldosteronism.