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Sudhakar Baluchamy Ye Zhang Prabakaran Ravichandran Vani Ramesh Ayodotun Sodipe Joseph C. Hall Olufisayo Jejelowo Daila S. Gridley Honglu Wu Govindarajan T. Ramesh 《Molecular and cellular biochemistry》2010,341(1-2):207-215
Exposure of living systems to radiation results in a wide assortment of lesions, the most significant of is damage to genomic DNA which alter specific cell functions including cell proliferation. The radiation induced DNA damage investigation is one of the important area in biology, but still the information available regarding the effects of proton is very limited. In this report, we investigated the differential gene expression pattern of DNA damage signaling genes such as damaged DNA binding, repair, cell cycle arrest, checkpoints and apoptosis using quantitative real-time RT-PCR in proton exposed mouse brain tissues. The expression profiles showed significant changes in DNA damage related genes in 2 Gy proton exposed mouse brain tissues as compared to control brain tissues. Furthermore, we also show that significantly increased levels of apoptotic related genes, caspase-3 and 8 activities in these cells, suggesting that in addition to differential expression of DNA damage genes, the alteration of apoptosis related genes may also contribute to the radiation induced DNA damage followed by programmed cell death. In summary, our findings suggest that proton exposed cells undergo severe DNA damage which in turn destabilize the chromatin stability. 相似文献
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Sudhakar Baluchamy Prabakaran Ravichandran Adaikkappan Periyakaruppan Vani Ramesh Joseph C. Hall Ye Zhang Olufisayo Jejelowo Daila S. Gridley Honglu Wu Govindarajan T. Ramesh 《The Journal of biological chemistry》2010,285(32):24769-24774
Radiation affects several cellular and molecular processes, including double
strand breakage and modifications of sugar moieties and bases. In outer space,
protons are the primary radiation source that poses a range of potential health
risks to astronauts. On the other hand, the use of proton irradiation for tumor
radiation therapy is increasing, as it largely spares healthy tissues while
killing tumor tissues. Although radiation-related research has been conducted
extensively, the molecular toxicology and cellular mechanisms affected by proton
irradiation remain poorly understood. Therefore, in this study, we irradiated
rat lung epithelial cells with different doses of protons and investigated their
effects on cell proliferation and death. Our data show an inhibition of cell
proliferation in proton-irradiated cells with a significant dose-dependent
activation and repression of reactive oxygen species and antioxidants
glutathione and superoxide dismutase, respectively, compared with control cells.
In addition, the activities of apoptosis-related genes such as caspase-3 and -8
were induced in a dose-dependent manner with corresponding increased levels of
DNA fragmentation in proton-irradiated cells compared with control cells.
Together, our results show that proton irradiation alters oxidant and
antioxidant levels in cells to activate the apoptotic pathway for cell
death. 相似文献
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Cui J Kaandorp JA Ositelu OO Beaudry V Knight A Nanfack YF Cunningham KW 《Cell calcium》2009,45(2):123-132
Yeast can proliferate in environments containing very high Ca(2+) primarily due to the activity of vacuolar Ca(2+) transporters Pmc1 and Vcx1. Yeast mutants lacking these transporters fail to grow in high Ca(2+) environments, but growth can be restored by small increases in environmental Mg(2+). Low extracellular Mg(2+) appeared to competitively inhibit novel Ca(2+) influx pathways and to diminish the concentration of free Ca(2+) in the cytoplasm, as judged from the luminescence of the photoprotein aequorin. These Mg(2+)-sensitive Ca(2+) influx pathways persisted in yvc1 cch1 double mutants. Based on mathematical models of the aequorin luminescence traces, we propose the existence in yeast of at least two Ca(2+) transporters that undergo rapid feedback inhibition in response to elevated cytosolic free Ca(2+) concentration. Finally, we show that Vcx1 helps return cytosolic Ca(2+) toward resting levels after shock with high extracellular Ca(2+) much more effectively than Pmc1 and that calcineurin, a protein phosphatase regulator of Vcx1 and Pmc1, had no detectable effects on these factors within the first few minutes of its activation. Therefore, computational modeling of Ca(2+) transport and signaling in yeast can provide important insights into the dynamics of this complex system. 相似文献
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Rosenzweig JA Jejelowo O Sha J Erova TE Brackman SM Kirtley ML van Lier CJ Chopra AK 《Applied microbiology and biotechnology》2011,91(2):265-286
Yersinia pestis (YP), the gram-negative plague bacterium, has shaped human history unlike any other pathogen known to mankind. YP (transmitted
by the bite of an infected flea) diverged only recently from the related enteric pathogen Yersinia pseudotuberculosis but causes radically different diseases. Three forms of plague exist in humans: bubonic (swollen lymph nodes or bubos), septicemic
(spread of YP through the lymphatics or bloodstream from the bubos to other organs), and contagious, pneumonic plague which
can be communicated via YP-charged respiratory droplets resulting in person–person transmission and rapid death if left untreated
(50–90% mortality). Despite the potential threat of weaponized YP being employed in bioterrorism and YP infections remaining
prevalent in endemic regions of the world where rodent populations are high (including the four corner regions of the USA),
an efficacious vaccine that confers immunoprotection has yet to be developed. This review article will describe the current
vaccine candidates being evaluated in various model systems and provide an overall summary on the progress of this important
endeavor. 相似文献
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Prabakaran Ravichandran Adaikkappan Periyakaruppan Bindu Sadanandan Vani Ramesh Joseph C. Hall Olufisayo Jejelowo Govindarajan T. Ramesh 《Journal of biochemical and molecular toxicology》2009,23(5):333-344
Carbon nanotubes (CNTs), the most promising material with unique characteristics, find its application in different fields ranging from composite materials to medicine and from electronics to energy storage. However, little is known about the mechanism behind the interaction of these particles with cells and their toxicity. So, here we investigated the adverse effects of multiwalled CNTs (MWCNTs) in rat lung epithelial (LE) cells. The results showed that the incubation of LE cells with 0.5–10 μg/mL of MWCNTs caused a dose‐ and time‐dependent increase in the formation of free radicals, the accumulation of peroxidative products, the loss of cell viability, and antioxidant depletion. The significant amount of incorporation of dUTPs in the nucleus after 24 h confirms the induction of apoptosis. It was also observed that there is an increase in the activity of both caspases‐3 and caspase‐8 in cells, with increases in time and the concentration of MWCNTs. No significant incorporation of dUTPs was observed in cells, incubated with z‐VAD‐fmk , which confirmed the role of caspases in DNA fragmentation. The present study reveals that MWCNTs induced oxidative stress and stimulated apoptosis signaling pathway through caspase activation in rat LE cell lines. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:333–344, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20296 相似文献
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Tariq MA Soedipe A Ramesh G Wu H Zhang Y Shishodia S Gridley DS Pourmand N Jejelowo O 《Molecular and cellular biochemistry》2011,349(1-2):213-218
The space radiation environment consists of trapped particle radiation, solar particle radiation, and galactic cosmic radiation (GCR), in which protons are the most abundant particle type. During missions to the moon or to Mars, the constant exposure to GCR and occasional exposure to particles emitted from solar particle events (SPE) are major health concerns for astronauts. Therefore, in order to determine health risks during space missions, an understanding of cellular responses to proton exposure is of primary importance. The expression of DNA repair genes in response to ionizing radiation (X-rays and gamma rays) has been studied, but data on DNA repair in response to protons is lacking. Using qPCR analysis, we investigated changes in gene expression induced by positively charged particles (protons) in four categories (0, 0.1, 1.0, and 2.0 Gy) in nine different DNA repair genes isolated from the testes of irradiated mice. DNA repair genes were selected on the basis of their known functions. These genes include ERCC1 (5' incision subunit, DNA strand break repair), ERCC2/NER (opening DNA around the damage, Nucleotide Excision Repair), XRCC1 (5' incision subunit, DNA strand break repair), XRCC3 (DNA break and cross-link repair), XPA (binds damaged DNA in preincision complex), XPC (damage recognition), ATA or ATM (activates checkpoint signaling upon double strand breaks), MLH1 (post-replicative DNA mismatch repair), and PARP1 (base excision repair). Our results demonstrate that ERCC1, PARP1, and XPA genes showed no change at 0.1 Gy radiation, up-regulation at 1.0 Gy radiation (1.09 fold, 7.32 fold, 0.75 fold, respectively), and a remarkable increase in gene expression at 2.0 Gy radiation (4.83 fold, 57.58 fold and 87.58 fold, respectively). Expression of other genes, including ATM and XRCC3, was unchanged at 0.1 and 1.0 Gy radiation but showed up-regulation at 2.0 Gy radiation (2.64 fold and 2.86 fold, respectively). We were unable to detect gene expression for the remaining four genes (XPC, ERCC2, XRCC1, and MLH1) in either the experimental or control animals. 相似文献
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Nonapoptotic death of Saccharomyces cerevisiae cells that is stimulated by Hsp90 and inhibited by calcineurin and Cmk2 in response to endoplasmic reticulum stresses 下载免费PDF全文
Endoplasmic reticulum (ER) stress can trigger apoptosis and necrosis in many types of mammalian cells. Previous studies in yeast found little or no cell death in response to the ER stressor tunicamycin, but a recent study suggested widespread apoptosis-like death. Here we show that wild-type laboratory Saccharomyces cerevisiae cells responding to tunicamycin die by nonapoptotic mechanisms in low-osmolyte culture media and survive for long periods of time in standard synthetic media. Survival requires calcineurin, a Ca(2+)/calmodulin-dependent protein phosphatase, but none of its known targets. The Ca(2+)/calmodulin-dependent protein kinase Cmk2 was identified as an indirect target of calcineurin that suppresses death of calcineurin-deficient cells. Death of Cmk2- and/or calcineurin-deficient S. cerevisiae cells was preceded by accumulation of reactive oxygen species but was not associated with hallmarks of apoptosis and was not dependent on Mca1, Aif1, Nuc1, or other factors implicated in apoptosis-like death. Cmk2 and calcineurin also independently suppressed the death of S. cerevisiae cells responding to dithiothreitol or miconazole, a common azole-class antifungal drug. Though inhibitors of Hsp90 have been shown to diminish calcineurin signaling in S. cerevisiae and to synergistically inhibit growth in combination with azoles, they did not stimulate death of S. cerevisiae cells in combination with miconazole or tunicamycin, and instead they prevented the death of calcineurin- and Cmk2-deficient cells. These findings reveal a novel prodeath role for Hsp90 and antideath roles for calcineurin and Cmk2 that extend the life span of S. cerevisiae cells responding to both natural and clinical antifungal compounds. 相似文献