Acute lung injury (ALI) as a serious diseases with high mortality and is considered a threat to human health and life. A number of studies have focused on the treatment and prevention of lung injury. However, the molecular mechanisms responsible for the development of lung injury are not yet fully understood, and this has impeded the development of effective drugs and treatment strategies.
View Article and Find Full Text PDFTNKS1BP1 was originally identified as an interaction protein of tankyrase 1, which belongs to the poly(ADP-ribose) polymerase (PARP) superfamily. PARP members play important roles for example in DNA repair, telomere stability and mitosis regulation. Although the TNKS1BP1 protein was considered to be a poly(ADP-ribosyl)ation acceptor of tankyrase 1, its function is still unknown.
View Article and Find Full Text PDFInt J Biol Sci
September 2013
The p53-inducible gene 3 (PIG3) recently has been reported to be a new player in DNA damage signaling and response, but the crucial mechanism remains unclear. In the present study, the potential mechanism of PIG3 participation in the DNA damage response induced by ionizing radiation (IR) was investigated in multiple cell lines with depleted expression of PIG3 transiently or stably by the small interference RNA and lentivirus-mediated shRNA expression strategies. PIG3 knockdown led to an abnormal DNA damage response, including decreased IR-induced phosphorylation of H2AX, Chk1, Chk2 and Kap-1 as well as a prolonged G2-M arrest and aberrant mitotic progression.
View Article and Find Full Text PDFObjectives: To investigate the impact of tracheal mucosa involvement on the clinical features of sarcoidosis.
Methods: The clinical data of sarcoidosis patients with (Group A, n = 26) and without (Group B, n = 61) tracheal mucosa involvement were evaluated retrospectively.
Results: The proportion of patients suffering from cough in Group A was 92.
Mitotic catastrophe, a form of cell death resulting from abnormal mitosis, is a cytotoxic death pathway as well as an appealing mechanistic strategy for the development of anti-cancer drugs. In this study, 6-bromine-5-hydroxy-4-methoxybenzaldehyde was demonstrated to induce DNA double-strand break, multipolar spindles, sustain mitotic arrest and generate multinucleated cells, all of which indicate mitotic catastrophe, in human hepatoma HepG2 cells. We used proteomic profiling to identify the differentially expressed proteins underlying mitotic catastrophe.
View Article and Find Full Text PDFBackground: Overexpression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is commonly occurred in cancers and causes radioresistance and poor prognosis. In present study, the single-chain variable antibody fragments (scFv) targeting DNA-PKcs was developed for the application of radiosensitization in vitro and in vivo. A humanized semisynthetic scFv library and the phage-display antibodies technology were employed to screen DNA-PKcs scFv antibody.
View Article and Find Full Text PDFDNA-dependent protein kinase catalytic subunit (DNA-PKcs) is well known as a critical component involving the nonhomologous end joining pathway of DNA double-strand breaks repair. Here, we showed another important role of DNA-PKcs in stabilizing spindle formation and preventing mitotic catastrophe in response to DNA damage. Inactivation of DNA-PKcs by small interfering RNA or specific inhibitor NU7026 resulted in an increased outcome of polyploidy after 2-Gy or 4-Gy irradiation.
View Article and Find Full Text PDFObjective: To observe the anti-proliferation effect of bevacizumab and SN-38 (active metabolite of irinotecan), and investigate the possible mechanisms of these two agents.
Methods: Human colon cancer LoVo cells were cultured under hypoxic conditions. Inhibition of cell proliferation was evaluated by MTT assay.
Cyclin B1, an important cell cycle regulator, was up-regulated in lymphocytes of human immunodeficiency virus (HIV)-infected patients. However, the mechanism of cyclin B1 up-regulation and the effects of the up-regulation on the host cells remain unclear. Here, we show that HIV-encoded Tat protein regulates cyclin B1 levels in two different ways: first, Tat stimulates the transcription of cyclin B1, which increases cyclin B1 levels and promotes the cells apoptosis; and second, Tat stimulates polyubiquitination-mediated degradation of cyclin B1 through binding to the N-terminal of cyclin B1 (aa 61-129) that is just downstream of the D box, which prevents excessive levels of cyclin B1 in the cells.
View Article and Find Full Text PDFThe immediate-early response gene 5 (IER5) was previously shown, using microarray analysis, to be upregulated by ionizing radiation. Here we further characterized the dose- and time-dependency of radiation-induced expression of IER5 at doses from 0.5 to 15 Gy by quantitative real-time PCR analyses in HeLa cells and human lymphoblastoid AHH-1 cells.
View Article and Find Full Text PDFBackground: C-Myc is a short-lived oncoprotein that is destroyed by ubiquitin-mediated proteolysis. Dysregulated accumulation of c-Myc commonly occurs in human cancers. Some of those cases with the dysregulated c-Myc protein accumulation are attributed to gene amplification or increased mRNA expression.
View Article and Find Full Text PDFVanillin is a naturally occurring compound and food-flavoring agent with antioxidant and antimutagenic activities. In present study, we explored the radioprotective effect of a novel vanillin derivative VND3207 (4-hydroxy-3,5-dimethoxybenzaldehyde). VND3207 has a much higher potential in scavenging hydroxyl radical and superoxide radical than vanillin as indicated in the ESR spin-trapping measurement, and it can effectively protect plasmid DNA against 10-50 Gy gamma-ray induced breaks in vitro at the concentrations as low as 10-20 microM.
View Article and Find Full Text PDFNan Fang Yi Ke Da Xue Xue Bao
September 2007
Objective: To study the effect of the small interfering RNA (siRNA)-mediated LKB1 gene silencing on the biological behavior of lung carcinoma cells.
Methods: RNA interference technique was used to silence LKB1 gene in lung carcinoma cells, and the expression of LKB1 protein were subsequently detected by Western blotting. The cell proliferation was then assessed by observing the growth curve and clone formation of the cells, and cell cycle and apoptosis were assayed by flow cytometry.
The sensitivity of cancer cells as well as normal cells in response to ionizing radiation (IR) is believed to be associated with the early inducible expression of specific genes. Using cDNA microarray technology, here we explored and compared the global transcriptional changes in human lymphoblastoid AHH-1 cells irradiated with 0.05-, 0.
View Article and Find Full Text PDFVanillin, a naturally occurring food component, has been reported to have anti-mutagenic and anti-metastatic potentials, and to inhibit DNA-PKcs activity. However, vanillin itself exhibits very weak antiproliferative activity. We explored the effects of bromovanin (6-bromine-5-hydroxy-4-methoxybenzaldehyde), a novel vanillin derivative, on survival and cell-cycle progression of human Jurkat leukemia cells.
View Article and Find Full Text PDFInt J Radiat Oncol Biol Phys
July 2006
Purpose: There is accumulating evidence that cancer patients with human immmunodeficiency virus-1/acquired immunodeficency syndrome (HIV-1/AIDS) have more severe tissue reactions and often develop cutaneous toxic effects when subjected to radiotherapy. Here we explored the effects of the HIV-1 Tat protein on cellular responses to ionizing radiation.
Methods And Materials: Two Tat-expressing cell lines, TT2 and TE671-Tat, were derived from human rhabdomyosarcoma cells by transfecting with the HIV-1 tat gene.
DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a member of a sub-family of phosphoinositol 3-kinases, has been reported overexpressed in various human cancers, but its significance is unclear. In the present study, we generated the stable cell line HeLa(siRNAH1) of silenced DNA-PKcs by transfecting HeLa cells with the siRNA construct targeting the catalytic motif of DNA-PKcs. The expression of DNA-PKcs was markedly suppressed in HeLa(siRNAH1) cells, and eventuating in increased cellular sensitivity to ionizing radiation as well as cisplatin.
View Article and Find Full Text PDFZhonghua Zhong Liu Za Zhi
September 2004
Objective: To study the effect of overexpression of Smad7 gene on cell proliferation in human bronchial epithelial cell lines.
Methods: Human bronchial epithelial cell lines, BEP2D and BERP35T2 cells, were cotransfected with the mammalian expression vectors PCISmad7.neo and pMyc-SEAP, the latter was ac-myc cis-acting enhancer element fused with alkaline phosphatase (SEAP) reporter gene.