Ni2+-enhanced charge transport via π-π stacking corridor in metallic DNA.

The mechanism underlying DNA charge transport is intriguing. However, poor conductivity of DNA makes it difficult to detect DNA charge transport. Metallic DNA (M-DNA) has better conducting properties than native DNA. Ni(2+) may chelate in DNA and thus enhance DNA conductivity. On the basis of this finding, it is possible to reveal the mechanisms underlying DNA charge transport. The conductivity of various Ni-DNA species such as single-stranded, full complement, or mismatched sequence molecules was systematically tested with ultraviolet absorption and electrical or chemical methods. The results showed that the conductivity of single-stranded Ni-DNA (Ni-ssDNA) was similar to that of a native DNA duplex. Moreover, the resistance of Ni-DNA with a single basepair mismatch was significantly higher than that of fully complementary Ni-DNA duplexes. The resistance also increased exponentially as the number of mismatched basepairs increased linearly after the tunneling current behavior predicted by the Simmons model. In conclusion, the charges in Ni(2+)-doped DNA are transported through the Ni(2+)-mediated π-π stacking corridor. Furthermore, Ni-DNA acts as a conducting wire and exhibits a tunneling barrier when basepair mismatches occur. This property may be useful in detecting single basepair mismatches.

Cell size control by ovarian factors regulates juvenile hormone synthesis in corpora allata of the cockroach, Diploptera punctata.

The corpora allata synthesize and release juvenile hormone (JH) that in turn regulates insect growth, metamorphosis and reproduction. In the corpus allatum (CA) of the female adult cockroach Diploptera punctata, cyclic rise and decline in JH synthesis rates occur concurrently with cyclic growth and atrophy during an ovarian cycle. Here, we report that protein content decreases, whereas Golgi population, lysosomal content and autophagic activities increase with decrease in CA cell size. Also, the concentration of cyclic GMP (cGMP) is low in large cells and high in small cells. Results of treating CA with ovarian tissue suggest that a putative peptidergic growth regulator released from mature ovaries acts directly on active CA cells and induces the elevation of intracellular cGMP content. Consequently, elevated cGMP may inhibit protein synthesis or trigger massive and synchronous autophagic activities, resulting in cell atrophy and reduction of protein content. As a result of the depletion of cellular machinery, CA glands exhibit long-term depression in JH synthesis.

Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells.

Gefitinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), has been used to treat numerous cancers; however, evidence has shown that cancer cells can become resistant to gefitinib during therapy. Here, we report a human proto-oncogene, securin, which displays resistance to death in cancer cells. Gefitinib treatment decreases securin levels at the protein level by inducing protein instability but did not affect on the securin gene expression. Treatment with gefitinib induced cytotoxicity in various human cancer cell types, including RKO (colon cancer), A549 (lung cancer), BFTC905 (bladder cancer), MCF7 (breast cancer) and A375 (skin cancer). BFTC905 and A549 cells expressed relatively high levels of the phosphorylated and total EGFR proteins; however, A375, MCF7 and RKO cells did not markedly express these proteins. Moreover, following treatment with gefitinib, the securin-wild type cancer cells were more resistant to apoptotic induction than the securin-null cancer cells. Surprisingly, both the securin-wild type and securin-null cancer cells expressed the EGFR protein at similar levels. Treatment with gefitinib induced mitochondrial dysfunction, cytochrome c release, caspase-3 activation and poly (ADP-ribose) polymerase protein cleavage, indicating that apoptosis occurred in these cancer cells. The transfection of a GPF-securin expression vector increased both the proliferation rates and resistance to gefitinib-induced death in these cancer cells. Taken together, these findings demonstrate that the presence of securin promotes resistance to gefitinib-induced apoptosis via an EGFR-independent pathway in human cancer cells.

Ni(2+) doping DNA: a semiconducting biopolymer.

DNA is a one-dimensional nanowire in nature, and it may not be used in nanodevices due to its low conductivity. In order to improve the conducting property of DNA, divalent Ni(2+) are incorporated into the base pairs of DNA at pH≥8.5 and nickel DNA (Ni-DNA) is formed. Conducting scanning probe microscopy (SPM) analysis reveals that the Ni-DNA is a semiconducting biopolymer and the Schottky barrier of Ni-DNA reduces to 2 eV. Meanwhile, electrochemical analysis by cyclic voltammetry and AC impedance shows that the conductance of Ni-DNA is better than that of native DNA by a factor of approximately 20-fold. UV spectroscopy and DNA base pair mismatch analyses show that the conducting mechanism of Ni-DNA is due to electrons hopping through the π-π stacking of DNA base pairs. This biomaterial is a designable one-dimensional semiconducting polymer for usage in nanodevices.

Activation of p38 mitogen-activated protein kinase by celecoxib oppositely regulates survivin and gamma-H2AX in human colorectal cancer cells.

Cancer cells express survivin that facilitates tumorigenesis. Celecoxib has been shown to reduce human colorectal cancers. However, the role and regulation of survivin by celecoxib in colorectal carcinoma cells remain unclear. Treatment with 40-80 muM celecoxib for 24 h induced cytotoxicity and proliferation inhibition via a concentration-dependent manner in RKO colorectal carcinoma cells. Celecoxib blocked the survivin protein expression and increased the phosphorylation of H2AX at serine-193 (gamma-H2AX). The survivin gene knockdown by transfection with a survivin siRNA revealed that the loss of survivin correlated with the expression of gamma-H2AX. Meanwhile, celecoxib increased caspase-3 activation and apoptosis. Celecoxib activated the phosphorylation of p38 mitogen-activated protein (MAP) kinase. The phosphorylated proteins of p38 MAP kinase and gamma-H2AX were observed in the apoptotic cells. SB203580, a specific p38 MAP kinase inhibitor, protected the survivin protein expression and decreased the levels of gamma-H2AX and apoptosis in the celecoxib-exposed cells. The blockade of survivin expression increased the celecoxib-induced cytotoxicity; conversely, overexpression of survivin by transfection with a survivin-expressing vector raised the cancer cell proliferation and resisted the celecoxib-induced cell death. Our results provide for the first time that p38 MAP kinase participates in the down-regulation of survivin and subsequently induces the activation of gamma-H2AX for mediating apoptosis following treatment with celecoxib in human colorectal cancer cells.