Mitogen-induced transcriptional programming in human fibroblasts.

Treatment of serum-starved quiescent human cells with fetal bovine serum (FBS), epidermal growth factor (EGF), or the phorbol ester (12-O-tetradecanoylphorbol-13-acetate, TPA) activates the RAS-MAPK pathway which initiates a transcriptional program which drives cells toward proliferation. Stimulation of the RAS-MAPK pathway activates mitogen- and stress-activated kinases (MSK) 1 and 2, which phosphorylate histone H3 at S10 (H3S10ph) or S28 (H3S28ph) (nucleosomal response) located at the regulatory regions of immediate-early genes, setting in motion a series of chromatin remodeling events that result in transcription initiation. To investigate immediate-early genes regulated by the MSK, we have completed transcriptome analyses (RNA sequencing) of human normal fibroblast cells (CCD-1070Sk) stimulated with EGF or TPA ± H89, a potent MSK/PKA inhibitor. The induction of many immediate-early genes was independent of MSK activity. However, the induction of immediate-early genes attenuated with H89 also had reduced induction with the PKA inhibitor, Rp-cAMPS. Several EGF-induced genes, coding for transcriptional repressors, were further upregulated with H89 but not with Rp-cAMPS, suggesting a role for MSK in modulating the induction level of these genes.

Mitogen and stress- activated protein kinase regulated gene expression in cancer cells.

The mitogen- and stress-activated protein kinases activated by the extracellular-signal-regulated kinase 1/2 and/or stress-activated protein kinase 2/p38 mitogen-activated protein kinase pathways are recruited to the regulatory region of a subset of genes termed immediate-early genes, often leading to their induction. These genes, many of which code for transcription factors, have been directly linked to the phenotypic events in carcinogenesis. In this paper, we focus on the mitogen- and stress-activated protein kinases; their discovery, activation, H3 phosphorylation and recent discoveries in their roles in cancer.

Silver nanoparticles influenced rat serum metabolites and tissue morphology.

BACKGROUND: Silver nanoparticles (AgNPs) are increasingly and extensively being applied for biomedical purposes. However, studies on the safety/toxicity profiles of AgNPs are limited. This necessitates the further studies in this direction. Here, we studied the effect of AgNP administration on rat serum metabolites and tissue morphology. METHODS: Rats were randomly distributed into eight groups of five animals each. Oral administration of AgNPs to rats at 100, 1000, and 5000 mg/kg was done daily and carried out for 7, 14, and 21 days alternately. The control received distilled water. Animals were sacrificed under diethyl ether anesthesia 24 h after cessation of last treatments. The blood and vital organs were harvested and prepared for biochemical and histopathology examinations, respectively. RESULTS: Data revealed that AgNP administration at the different dosages caused elevated serum urea and creatinine levels. On the other hand, levels of inorganic phosphate in rat serum following administration of AgNPs were significantly (p<0.05) reduced. Also, administration at 1000 and 5000 mg/kg AgNPs in rats decreased serum levels of sodium. In contrast, AgNP administration in rats caused elevated (p<0.05) serum potassium levels. The histopathological presentations show diverse inimical alterations to cellular architecture in rats administered with AgNPs. CONCLUSIONS: We show evidence suggesting that AgNPs may have potential to adversely affect the kidney functions as well as capability to cause myriad of cellular damage.

Biochemical Evaluation of Silver Nanoparticles in Wistar Rats.

Background. Silver nanoparticles have found wider and increasing biomedical applications due to their broad antimicrobial characteristics. However, toxicity of nanoparticles is a subject of continued controversy, thus necessitating further studies in this direction. Objectives. This study investigated the biochemical effects of silver nanoparticles in Wistar rats. Materials and Methods. Forty male rats were randomly distributed into eight experimental groups of five. Group A served as the control and received distilled water. Groups B to H were orally exposed to varying concentrations of silver nanoparticles (AgNPs) at 100, 1000, and 5000 mg/kg daily for 7, 14, and 21 days alternately. Following cessation of treatments, rats were sacrificed and the blood and other vital organs were collected and prepared as specimens for biochemical analysis. Results. Administration of AgNPs to rats did not produce significant loss in feed intake and body weight. However, rat exposure to AgNPs caused significant alterations to levels of serum and tissue AST, ALT, and ALP. At the 100 mg/kg AgNPs exposure, rat serum and tissue AST and ALT levels were significantly decreased (P < 0.05). In contrast, AgNPs administration elevated (P < 0.05) ALP levels in rat serum and tissues. Conclusion. We show evidence that AgNPs administration to Wistar rats altered some biochemical parameters.