A review on interplay between small RNAs and oxidative stress in cancer progression

Molecular and Cellular Biochemistry - Oxidative stress has been known to be the underlying cause in many instances of cancer development. The new aspect of cancer genesis that has caught the...     

Mechanism of Silver Nanoparticles Action on Insect Pigmentation Reveals Intervention of Copper Homeostasis

Silver nanoparticles (AgNPs), like almost all nanoparticles, are potentially toxic beyond a certain concentration because the survival of the organism is compromised due to scores of pathophysiological abnormalities past that concentration. However, the mechanism of AgNP toxicity remains undetermined. Instead of applying a toxic dose, we attempted to monitor the effects of AgNPs at a nonlethal concentration on wild type Drosophila melanogaster by exposing them throughout their development. All adult flies raised in AgNP doped food showed that up to 50 mg/L concentration AgNP has no negative influence on median survival; however, these flies appeared uniformly lighter in body color due to the loss of melanin pigments in their cuticle. Additionally, fertility and vertical movement ability were compromised due to AgNP feeding. Determination of the amount of free ionic silver (Ag⁺) led us to claim that the observed biological effects have resulted from the AgNPs and not from Ag⁺. Biochemical analysis suggests that the activity of copper dependent enzymes, namely tyrosinase and Cu-Zn superoxide dismutase, are decreased significantly following the consumption of AgNPs, despite the constant level of copper present in the tissue. Consequently, we propose a mechanism whereby consumption of excess AgNPs in association with membrane bound copper transporter proteins cause sequestration of copper, thus creating a condition that resembles copper starvation. This model also explains the cuticular demelanization effect resulting from AgNP since tyrosinase activity is essential for melanin biosynthesis. Finally, we claim that Drosophila, an established genetic model system, can be well utilized for further understanding of the biological effects of nanoparticles.     

Fatty acid-induced angiogenesis in first trimester placental trophoblast cells: Possible roles of cellular fatty acid-binding proteins

Angiogenesis is involved in the growth of new blood vessels from the existing one. Consequently, angiogenesis plays an indispensable role in tissue growth and repair including early placentation processes. Besides angiogenic growth factors (vascular endothelial growth factor (VEGF), angiopoietin-like 4 (ANGPTL4), placental growth factor (PlGF), platelet derived growth factor (PDGF), fibroblast growth factors (FGF)), dietary fatty acids (c>16) also directly or indirectly modulate angiogenic processes in tumors and other cell systems. Usually n − 3 fatty acids inhibit whereas n − 6 fatty acids stimulate angiogenesis in tumors and other cells. Contrary to this, docosahexaenoic acid, 22:6n − 3 (DHA) and other fatty acids including conjugated linoleic acid stimulate angiogenesis in placental first trimester cells. In addition to the stimulation of expression of major angiogenic factors such as VEGF and ANGPTL4, fatty acids also stimulate expression of intracellular fatty acid-binding proteins (FABPs) FABP-4 and FABP-3 those are known to directly modulate angiogenesis. Emerging data indicate that FABPs may be involved in the angiogenesis process. This paper reviews the fatty acid mediated angiogenesis process and the involvement of their binding proteins in these processes.     

A Sod2 null mutation confers severely reduced adult life span in Drosophila

A null mutation for the Sod2 gene, Sod2n283, was obtained in Drosophila melanogaster. Homozygous Sod2 null (Sodn283/Sodn283) adult flies survive up to 24 hr following eclosion, a phenotype reminiscent of mice, where Sod2-/- progeny suffer neonatal lethality. Sodn283/+ heterozygotes are sensitive to oxidative stress induced by paraquat treatment.     

Postprandial activation of hemostatic factors: role of dietary fatty acids

Intake of dietary fat is an important determinant of the plasma concentration of triacylglycerol-rich lipoproteins, and the degree of alimentary lipemia is reported to have effects on hemostatic status including platelet function. Although association between the amount of dietary fat intake, lipemic response and certain cardiovascular disease (CVD) risk factors (VIIa and PAI-1) has been reported, the significance of the fatty acid composition of ingested fat for the postprandial lipid concentrations and the hemostatic factors is still unclear. Accumulating evidence suggests a relationship between dietary fatty acids and emerging hemostatic CVD risk factors, although much of this evidence is incomplete or conflicting. In order to improve our knowledge in this area, sufficient sample size in future studies are required to take into account of the genetic variation (gene polymorphisms for VII, PAI-1), sex, physical activity, stage of life factors, and sufficient duration to account for adaptation for definitive conclusions.     

Up-regulated P21CIP1 expression is part of the regulation quantitatively controlling serum deprivation-induced apoptosis

Among the many genes which have been suggested to be required by the molecular mechanism dictating apoptotic death, some have been shown to function as pacemakers to pave the way for cells either to live or to die. Previously we have shown that immediate early gene expressions associated with the G₁ phase of cell cycle traverse are candidates for this function. Here we report that the well-known key regulator for halting cell cycling at the G₁/S border, the p21 protein known as WAF1, Cip1, Pic1, or Sdi1, is also involved in the execution of cells' suicidal death. p21 up-regulation is seen in quiescent mouse 3T3 fibroblasts stimulated to die by serum deprivation, at both message and protein levels, evidenced by increased protein presence in its targeted functional site, the nucleus. In addition, we show that this up-regulation of p21 is functionally related to the operational efficiency of the apoptotic process, in that when cells are stably transfected with an antisense construct to repress the endogenous p21-protein level, death is delayed. Quantitative protection from apoptosis with antisense p21 transfection is relatively proportional to the repressed level of this protein in the cells. Taken together, our results suggest that the apoptosis-dependent additional increase of p21 beyond the base level, seen in serum-deprived quiescent cells, may be involved in the molecular events precipitating a rapid program of cell demise, and that repression of this increase may obstruct the operation of this program and postpone the eventual death. J. Cell. Biochem. 64:434–446. © 1997 Wiley-Liss, Inc.