The human hepatoma HepG2 cell line was chosen as a representative of solid tissue-derived cell systems in which folate metabolism and apoptosis induction have not been thoroughly investigated. HepG2 cells were cultivated in the control or folate-deficient media (control media lacking of folate, glycine, thymidine and hypoxanthine) for 4 wk. This resulted in a decrease in intracellular folate levels to 32% of the control within 1 wk, which was followed by growth arrest and greater cell death rates. These disturbances of folate deficiency coincided with apoptotic induction, as characteristically shown by nucleosomal DNA fragmentation of 180-200 base pair multimers, nuclear chromatin condensation and positive terminal transferase-mediated dUTP nick end labeling assay. Apoptosis coincided with an accumulation of cells in S-phase, a subsequent G2/M phase block and a significant increase in mean protein content as evaluated by flow cytometric analyses employing a double-staining method. The growth and cell cycle arrest under folate-deficient conditions was independent of a change of p53 expression as measured by an enzyme-linked immunosorbent assay. Supplementation of 2 micromol/L folate normalized cell cycles and diminished DNA fragmentation. Taken together, these data indicate that HepG2 cells cultivated in folate-deficient medium have a low folate concentration, decreased growth and viability, and increased apoptotic propensity. This occurrence of apoptosis was associated with a cell cycle-specific mechanism and independent of p53-mediated pathway.
We consider a semilinear elliptic system with both concave-convex nonlinearities and critical growth terms in bounded domains. The existence and multiplicity results of positive solutions are obtained by variational methods.
Variational methods are used to prove the multiplicity of positive solutions for the following singular elliptic equation:where 0 ∈ Ω ⊂ ℝN, N ≥ 3, is a bounded domain with smooth boundary ∂ Ω, λ > 0 , $1\le q<2$, $0\le\mu<\bar{\mu}=(N-2)^2/4$, 0 ≤ s < 2, 2*(s)=2(N−s)/(N−2) and f and g are continuous functions on $\bar{\varOmega}$, that change sign on Ω.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.