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Albi E.,Laboratory of Nuclear Lipid BioPathology | Curcio F.,University of Udine | Spelat R.,University of Udine | Lazzarini A.,Laboratory of Nuclear Lipid BioPathology | And 5 more authors.
Astrobiology | Year: 2012

This is a case report of apparent thyroid structural and functional alteration in a single mouse subjected to low Earth orbit spaceflight for 91 days. Histological examination of the thyroid gland revealed an increase in the average follicle size compared to that of three control animals and three animals exposed to hypergravity (2g) conditions. Immunoblotting analysis detected an increase in two thyroid gland enzymes, sphingomyelinase and sphingomyelin-synthase1. In addition, sphingomyelinase, an enzyme confined to the cell nucleus in the control animals, was found in the mouse exposed to hypogravity to be homogeneously distributed throughout the cell bodies. It represents the first animal observation of the influence of weightlessness on sphingomyelin metabolism. Key Words: Gravity-Lipid-Spaceflight-Sphingomyelin- Thyroid. Astrobiology 12, 1035-1041. © Copyright 2012, Mary Ann Liebert, Inc. 2012. Source

Albi E.,Laboratory of Nuclear Lipid BioPathology | Ambesi-Impiombato F.S.,University of Udine | Lazzarini A.,Laboratory of Nuclear Lipid BioPathology | Lazzarini A.,University of Udine | And 6 more authors.
Astrobiology | Year: 2014

During space missions, astronauts work in a state of separation from their daily social environment and in physical confinement. It has been shown that confinement influences mood and brain cortical activity, but no data has been obtained with regard to its effect on the thyroid gland, the structure and function of which change during spaceflights. Here, we report the results of a study on the effects of confinement on mouse thyroid, which was implemented with the Mice Drawer System Facility maintained on the ground, a system used for spaceflight experiments. The results show that confinement changes the microscopic structure of the thyroid gland and that it exhibits symptoms similar to those that result from physiological and/or pathological hyperfunction. What is left unchanged, however, is the sphingomyelinase-thyrotropin receptor relationship, which is important for thyrotropin response with a consequential production of hormones that act on the metabolism of almost all tissues and reduces the production of calcitonin, a hormone involved in bone metabolism. During space missions, the overexpression of pleiotrophin, a widespread cytokine up-regulated after tissue injury that acts on bone remodeling, attenuates changes to the thyroid that are spaceflight-dependent; therefore we studied the thyroids of pleiotrophin-transgenic mice in the Mice Drawer System Facility. In confinement, pleiotrophin overexpression does not protect from the loss of calcitonin. The contribution of confinement to thyroid damage during spaceflights is discussed. © Copyright 2014, Mary Ann Liebert, Inc. 2014. Source

Codini M.,University of Perugia | Cataldi S.,University of Perugia | Ambesi-Impiombato F.S.,University of Udine | Lazzarini A.,Laboratory of Nuclear Lipid BioPathology | And 5 more authors.
International Journal of Molecular Sciences | Year: 2015

The use of gentamicin for the treatment of bacterial infection has always been an interesting and highly speculated issue for the scientific community. Conversely, its effect on cancer cells has been very little investigated. We studied the effect of high doses of gentamicin on non-Hodgkin’s T-cell human lymphoblastic lymphoma (SUP-T1). We showed that gentamicin delayed cell growth and induced cell death in lymphoma cells with a rather mild effect on lymphocytes. In SUP-T1 cells, GAPDH, B2M, CDKN1A and CDKN1B were down-expressed in comparison with lymphocytes. Gentamicin treatment in SUP-T1 cells restored the expression of GAPDH, B2M and CDKN1A to values similar to those of lymphocytes and caused overexpression of CDKN1B. The drug acted via sphingomyelin metabolism; in whole cells, sphingomyelinase activity was stimulated, whereas in purified nuclei, sphingomyelinase activity was inhibited and that of sphingomyelin-synthase was stimulated, with a consequent high level of nuclear sphingomyelin content. We suggest that the increase of nuclear sphingomyelin might enrich the nucleus of lipid microdomains that act as a platform for active chromatin and, thus, might be responsible for gene expression. It is possible that in lymphoblastic lymphoma, high doses of gentamicin induce a beneficial therapeutic outcome. © 2015 by the authors; licensee MDPI, Basel, Switzerland. Source

Albi E.,Laboratory of Nuclear Lipid BioPathology | Curcio F.,University of Udine | Lazzarini A.,Laboratory of Nuclear Lipid BioPathology | Floridi A.,Laboratory of Nuclear Lipid BioPathology | And 5 more authors.
BioMed Research International | Year: 2014

After long-term exposure to real microgravity thyroid gland in vivo undergoes specific changes, follicles are made up of larger thyrocytes that produce more cAMP and express more thyrotropin-receptor, caveolin-1, and sphingomyelinase and sphingomyelin-synthase; parafollicular spaces lose C cells with consequent reduction of calcitonin production. Here we studied four immunohistochemical tumor markers (HBME-1, MIB-1, CK19, and Galectin-3) in thyroid of mice housed in the Mouse Drawer System and maintained for 90 days in the International Space Station. Results showed that MIB-1 proliferative index and CK19 are negative whereas HBME-1 and Galectin-3 are overexpressed. The positivity of Galectin-3 deserves attention not only for its expression but also and especially for its localization. Our results highlighted that, in microgravity conditions, Galectin-3 leaves thyrocytes and diffuses in colloid. It is possible that the gravity force contributes to the maintenance of the distribution of the molecules in both basal membrane side and apical membrane side and that the microgravity facilitates slippage of Galectin-3 in colloid probably due to membrane remodelling-microgravity induced. © 2014 Elisabetta Albi et al. Source

Codini M.,University of Perugia | Cataldi S.,University of Perugia | Lazzarini A.,Laboratory of Nuclear Lipid BioPathology | Tasegian A.,University of Perugia | And 7 more authors.
Lipids in Health and Disease | Year: 2016

Background: Diet and obesity are recognized in the scientific literature as important risk factors for cancer development and progression. Hypercholesterolemia facilitates lymphoma lymphoblastic cell growth and in time turns in hypocholesterolemia that is a sign of tumour progression. The present study examined how and where the cholesterol acts in cancer cells when you reproduce in vitro an in vivo hypercholesterolemia condition. Methods: We used non-Hodgkin's T cell human lymphoblastic lymphoma (SUP-T1 cell line) and we studied cell morphology, aggressiveness, gene expression for antioxidant proteins, polynucleotide kinase/phosphatase and actin, cholesterol and sphingomyelin content and finally sphingomyelinase activity in whole cells, nuclei and nuclear lipid microdomains. Results: We found that cholesterol changes cancer cell morphology with the appearance of protrusions together to the down expression of β-actin gene and reduction of β-actin protein. The lipid influences SUP-T1 cell aggressiveness since stimulates DNA and RNA synthesis for cell proliferation and increases raf1 and E-cadherin, molecules involved in invasion and migration of cancer cells. Cholesterol does not change GRX2 expression but it overexpresses SOD1, SOD2, CCS, PRDX1, GSR, GSS, CAT and PNKP. We suggest that cholesterol reaches the nucleus and increases the nuclear lipid microdomains known to act as platform for chromatin anchoring and gene expression. Conclusion: The results imply that, in hypercholesterolemia conditions, cholesterol reaches the nuclear lipid microdomains where activates gene expression coding for antioxidant proteins. We propose the cholesterolemia as useful parameter to monitor in patients with cancer. © 2016 Codini et al. Source

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