Publications (3)10.3 Total impact
-
Article: TGF-β signaling plays an important role in resisting γ-irradiation.
[show abstract] [hide abstract]
ABSTRACT: Transforming growth factor-β1 (TGF-β1) regulates various biological processes, including differentiation, bone remodeling and angiogenesis, and is particularly important as a regulator of homeostasis and cell growth in normal tissue. Interestingly, some studies have reported that TGF-β1 induces apoptosis through induction of specific genes, whereas others suggest that TGF-β1 inhibits apoptosis and facilitates cell survival. Resolving these discrepancies, which may reflect differences in cellular context, is an important research priority. Here, using the parental mink lung epithelial cell line, Mv1Lu, and its derivatives, R1B and DR26, lacking TGF-β receptors, we investigated the involvement of TGF-β signaling in the effects of γ-irradiation. We found that canonical TGF-β signaling played an important role in protecting cells from γ-irradiation. Introduction of functional TGF-β receptors or constitutively active Smads into R1B and DR26 cell lines reduced DNA fragmentation, caspase-3 cleavage and γ-H2AX foci formation in γ-irradiated cells. Notably, we also found that de novo protein synthesis was required for the radio-resistant effects of TGF-β1. Our data thus indicate that TGF-β1 protected against γ-irradiation, decreasing DNA damage and reducing apoptosis, and thereby enhanced cell survival.Experimental Cell Research 12/2012; · 3.58 Impact Factor -
Article: Substance P stimulates the recovery of bone marrow after the irradiation.
[show abstract] [hide abstract]
ABSTRACT: The therapeutic use of ionizing radiation (e.g., X-rays and γ-rays) needs to inflict minimal damage on non-target tissue. Recent studies have shown that substance P (SP) mediates multiple activities in various cell types, including cell proliferation, anti-apoptotic responses, and inflammatory processes. The present study investigated the effects of SP on γ-irradiated bone marrow stem cells (BMSCs). In mouse bone marrow extracts, SP prolonged activation of Erk1/2 and enhanced Bcl-2 expression, but attenuated the activation of apoptotic molecules (e.g., p38 and cleaved caspase-3) and down-regulated Bax. We also observed that SP-decreased apoptotic cell death and stimulated cell proliferation in γ-irradiated mouse bone marrow tissues through TUNEL assay and PCNA analysis. To determine how SP affects bone marrow stem cell populations, mouse bone marrow cells were isolated and colony-forming unit (CFU) of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) was estimated. SP-pretreated ones showed higher CFUs of MSC and HSC than untreated ones. Furthermore, when SP was pretreated in cultured human MSC, it significantly decreased apoptotic cells at 48 and 72 h after γ-irradiation. Compared with untreated cells, SP-treated human MSCs showed reduced cleavage of apoptotic molecules such as caspase-8, -9, -3, and poly ADP-ribose polymerase (PARP). Thus, our results suggest that SP alleviates γ-radiation-induced damage to mouse BMSCs and human MSCs via regulation of the apoptotic pathway.Journal of Cellular Physiology 10/2010; 226(5):1204-13. · 3.87 Impact Factor -
Article: Micronucleus-centromere assay and DNA repair gene polymorphism in lymphocytes of industrial radiographers.
[show abstract] [hide abstract]
ABSTRACT: The micronucleus-centromere assay using a pan-centromeric probe was used to assess chromosomal damage in lymphocytes of 47 industrial radiographers occupationally exposed to low dose ionizing radiation and 47 controls. The influence of genotype of DNA repair genes (XRCC1(399), XRCC3(241) and XPD(751)) on micronuclei (MN) frequency was also investigated. Centromere negative micronuclei (MNC-) frequency was significantly higher in radiographers than in controls, whereas similar centromere positive micronuclei (MNC+) frequency was observed in both groups. Poisson regression analyses revealed that the MNC- frequency was significantly associated with radiation occupational exposure and with cumulative-radiation doses in radiographers, after adjusting for confounding variables such as age, smoking, alcohol intake and genotypes. Compared to homozygous wild-type subjects, MNC- frequency in radiographers with variant XRCC3 genotype was significantly higher using univariate analysis. There were no differences in MNC- or MNC+ frequencies by genotype in controls. In conclusion, scoring of MNC- is a useful cytogenetic biomonitoring method for radiographers. Polymorphisms in XRCC3 might contribute to the increased genetic damage in individuals occupationally exposed to chronic ionizing radiation.Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 10/2009; 680(1-2):17-24. · 2.85 Impact Factor
