T-2 toxin, a major compound of trichothecenes, induces cell apoptosis and growth hormone (GH) deficiency and causes considerable growth retardation in animals and human cells. However, the mechanism underlying its growth suppression still remains unclear. Recent studies have suggested that ROS induced cell apoptosis and animal feed intake reduction, but there are limited reports on the role of RNS in T-2 toxin-mediated mitochondrial damage, cell apoptosis and growth retardation. Herein, T-2 toxin-induced GH3 cell damage and apoptosis were tested by MTT assay, LDH leakage and flow cytometry, respectively. Intracellular NO and antioxidant enzyme activity, ΔΨm, morphometric changes of mitochondria, the caspase pathway, and inflammatory factors were investigated. Free radical scavengers NAC, SOD and NO scavenger haemoglobin were used to explore the role of oxidative stress and the relationship between NO production and caspase pathway. The results clearly revealed that T-2 toxin caused significant increases in NO generation, cell apoptosis, GH deficiency, increased iNOS activity, upregulation of inflammatory factors and caspase pathway, decreases in ΔΨm and morphosis damage. These data suggest that mitochondria are a primary target of T-2 toxin-induced NO, and NO is a key mediator of T-2 toxin-induced cell apoptosis and GH deficiency via the mitochondria-dependent pathway in cells.

• MeSH
• adenohypofýza cytologie   MeSH
• apoptóza účinky léků   MeSH
• kaspasy metabolismus   MeSH
• krysa rodu rattus MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• oxid dusnatý metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• růstový hormon nedostatek   MeSH
• signální transdukce účinky léků   MeSH
• somatotropní buňky účinky léků   metabolismus   patologie   MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• T-2 toxin toxicita   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Ionizing radiation and somatostatin analogues are used for acromegaly treatment to achieve normalization or reduction of growth hormone hypersecretion and tumor shrinkage. In this study, we investigated a combination of somatostatin (SS14) with ionizing radiation of (60)Co and its effect on reparation of radiation-induced damage and cell death of somatomammotroph pituitary cells GH3. Doses of gamma-radiation 20-50 Gy were shown to inhibit proliferation and induce apoptosis in GH3 cells regardless of somatostatin presence. It has been found that the D(0) value for GH3 cells was 2.5 Gy. Somatostatin treatment increased radiosensitivity of GH3 cells, so that D(0) value decreased to 2.2 Gy. We detected quick phosphorylation of histone H2A.X upon irradiation by the dose 20 Gy and its colocalization with phosphorylated protein Nbs-1 in the site of double strand break of DNA (DSB). Number of DSB decreased significantly 24 h after irradiation, however, clearly distinguished foci persisted, indicating non repaired DSB, after irradiation alone or after combined treatment by irradiation and SS14. We found that SS14 alone triggers phosphorylation of Nbs1 (p-Nbs1), which correlates with antiproliferative effect of SS14. Irradiation also increased the presence of p-Nbs1. Most intensive phosphorylation of Nbs1 was detected after combined treatment of irradiation and SS14. The decrease of the number of the DSB foci 24 h after treatment shows a significant capacity of repair systems of GH3 cells. In spite of this, large number of unrepaired DSB persists for 24 h after the treatment. We conclude that SS14 does not have a radioprotective effect on somatomammotroph GH3 cells.

• MeSH
• adenom hypofýzy vylučující růstový hormon farmakoterapie   chirurgie   MeSH
• akromegalie farmakoterapie   chirurgie   MeSH
• apoptóza genetika   účinky záření   MeSH
• buněčný cyklus fyziologie   účinky záření   MeSH
• experimentální radiační poranění prevence a kontrola   MeSH
• histony metabolismus   účinky záření   MeSH
• ionizující záření MeSH
• jaderné proteiny metabolismus   účinky záření   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• nádorové buněčné linie MeSH
• nádory hypofýzy farmakoterapie   chirurgie   MeSH
• neparametrická statistika MeSH
• poškození DNA fyziologie   účinky léků   MeSH
• potkani Wistar MeSH
• proteiny buněčného cyklu metabolismus   účinky záření   MeSH
• radiochirurgie škodlivé účinky   MeSH
• somatostatin fyziologie   terapeutické užití   MeSH
• somatotropní buňky metabolismus   účinky léků   účinky záření   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH