19 research outputs found
External X-irradiation causes a decrease in the proliferation of two papillary thyroid carcinoma cell lines with no significant increase in cell death
Accelerated telomere attrition after oxidative stress in human cancer cell lines in the presence of Spirulina
Iodine deficiency induces a VEGF-dependent microvascular response in salivary glands and in the stomach
Despite efforts to optimize iodine supply in
iodine deficient countries, iodine deficiency (ID)
remains a global problem worldwide. Activation of the
local microvasculature by ID in the thyroid gland aims at
improving the local supply of iodide. For this purpose,
the thyrocytes secrete vascular endothelial growth factor
(VEGF) that acts on adjacent capillaries, via a reactive
oxygen species (ROS)/Hypoxia Inducible factor (HIF)-
dependent pathway. Beside the thyroid, other organs
including salivary glands and the stomach do express the
sodium/iodide symporter (NIS) and are able to take
iodide up, potentially rendering them sensitive to ID. To
verify this hypothesis, ID-induced effects on the local
microvasculature were studied in salivary glands and in
the stomach. ID was induced by feeding young mice
with an iodide-deficient diet and NIS inhibitor
perchlorate in the drinking water. In salivary glands, ID
induced a transient increase in HIF-1α protein
expression accompanied by a transient, VEGFdependent increase in blood flow. In the gastric mucosa,
ID transiently increased VEGF expression in the mucinsecreting epithelium and in ghrelin-secreting endocrine
cells. These observations suggest that microvascular
changes in response to ID occur in NIS-expressing
tissues other than the thyroid. NIS expressing cells could
be viewed as iodide sensors that respond to ID by
inducing vascular changes, probably to optimize iodide
bioavailability at regional or systemic levels
Ionizing radiation-induced gene modulations, cytokine content changes and telomere shortening in mouse fetuses exhibiting forelimb defects
AbstractSeveral lines of evidence have linked limb teratogenesis to radiation-induced apoptosis and to the p53 status in murine fetuses. In previous reports, we studied the occurrence of various malformations after intrauterine irradiation and showed that these malformations were modulated by p53-deficiency as well as by the developmental stage at which embryos were irradiated. In this new study, we focused onto one particular phenotype namely forelimb defects to further unravel the cellular and molecular mechanisms underlying this malformation.We measured various parameters expected to be directly or indirectly influenced by irradiation damage. The mouse fetuses were irradiated at day 12 p.c. (post conception) and examined for forelimb defects on gestational days 15, 16, 17 and 19 of development. The release of inflammatory cytokines was determined in the amniotic fluid on day 16 p.c. and the mean telomere lengths assessed at days 12, 13 and 19 p.c. Differential gene expression within the forelimb bud tissues was determined using Real Time quantitative PCR (RTqPCR) 24 h following irradiation. Apoptosis was investigated in the normal and malformed fetuses using the TUNEL assay and RTqPCR.First, we found that irradiated fetuses with forelimb defects displayed excessive apoptosis in the predigital regions. Besides, overexpression of the pro-apoptotic Bax gene indicates a mitochondrial-mediated cell death. Secondly, our results showed overexpression of MKK3 and MKK7 (members of the stress-activated MAP kinase family) within the malformed fetuses. The latter could be involved in radiation-induced apoptosis through activation of the p38 and JNK pathways. Thirdly, we found that irradiated fetuses exhibiting forelimb defects showed a marked telomere shortening. Interestingly, telomere shortening was observed as the malformations became apparent. Fourthly, we measured cytokine levels in the amniotic fluid and detected a considerable inflammatory reaction among the irradiated fetuses as evidenced by the increase in pro-inflammatory cytokine levels.Altogether, our data suggest that transcriptional modulations of apoptotic, inflammation, stress, and DNA damage players are early events in radiation-induced forelimb defects. These changes resulted in harsh developmental conditions as indicated by a marked increase in cytokine levels in the amniotic fluid and telomere shortening, two features concomitant with the onset of the forelimb defect phenotype in our study
Stress response and humoral immune system alterations related to chronic hypergravity in mice
Spaceflights are known to induce stress and immune dysregulation. Centrifugation, as hindlimb unloading, is a good ground based-model to simulate altered gravity which occurs during space missions. The aim of this study was to investigate the consequences of a long-term exposure to different levels of hypergravity on the stress response and the humoral immunity in a mouse model. For this purpose, adult C57Bl/6J male mice were subjected for 21 days either to control conditions or to 2G or 3G acceleration gravity forces. Corticosterone level and anxiety behavior revealed a stress response which was associated with a decrease of body weight, after 21-day of centrifugation at 3G but not at 2G. Spleen lymphocyte lipopolysaccharide (LPS) responsiveness was diminished by 40% in the 2G group only, whereas a decrease was noted when cells were stimulated with concanavalin A for both 2G and 3G groups (about 25% and 20%, respectively) compared to controls. Pro-inflammatory chemokines (MCP-1 and IP-10) and Th1 cytokines (IFNγ and IL2) were slightly decreased in the 2G group and strongly decreased in the 3G mouse group. Regarding Th2 cytokines (IL4, IL5) no further significant modification was observed, whereas the immunosuppressive cytokine IL10 was slightly increased in the 3G mice. Finally, serum IgG concentration was twice higher whereas IgA concentration was slightly increased (about 30%) and IgM were unchanged in 2G mice compared to controls. No difference was observed in the 3G group with these isotypes. Consequently, functional immune dysregulations and stress responses were dependent of the gravity level
Response to low-dose X-irradiation is p53-dependent in a papillary thyroid carcinoma model system
The link between high doses of radiation and thyroid cancer has been well established in various studies, as opposed to the effects of low doses. In this study, we investigated the effects of low-dose X-ray irradiation in a papillary thyroid carcinoma model with wild-type and mutated p53. A low dose of 62.5 mGy was enough to cause an upregulation of p16 and a decrease in the number of TPC-1 cells in the S phase, but not in the number of BCPAP p53-mutant cells. At a dose of 0.5 Gy, visible signs of senescence appeared only in the TPC-I cells. We conclude that low doses of X-rays are enough to cause a change in cell cycle distribution, possibly p53dependent p16 activation, but no significant apoptosis. Senescence requires higher doses of X-irradiation via a mechanism involving both p16 and p21