Radiation-induced bystander and systemic effects serve as a unifying model system for genotoxic stress responses

2018 ◽  
Vol 778 ◽  
pp. 13-22 ◽  
Author(s):  
Susanne Burdak-Rothkamm ◽  
Kai Rothkamm
Keyword(s):  
Stress Responses ◽  
Genotoxic Stress ◽  
Model System ◽  
Systemic Effects ◽  
Radiation Induced

scholarly journals A Kinase-Independent Role for Cyclin-Dependent Kinase 19 in p53 Response

2017 ◽  
Vol 37 (13) ◽  
Author(s):  
K. Audrey Audetat ◽  
Matthew D. Galbraith ◽  
Aaron T. Odell ◽  
Thomas Lee ◽  
Ahwan Pandey ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Stress Responses ◽  
Cholesterol Metabolism ◽  
Genotoxic Stress ◽  
General Factor ◽  
Cyclin Dependent Kinase ◽  
Genome Wide ◽  
P53 Response ◽  
P53 Target Gene ◽  
Rna Polymerase Ii Transcription

ABSTRACT The human Mediator complex regulates RNA polymerase II transcription genome-wide. A general factor that regulates Mediator function is the four-subunit kinase module, which contains either cyclin-dependent kinase 8 (CDK8) or CDK19. Whereas CDK8 is linked to specific signaling cascades and oncogenesis, the cellular roles of its paralog, CDK19, are poorly studied. We discovered that osteosarcoma cells (SJSA) are naturally depleted of CDK8 protein. Whereas stable CDK19 knockdown was tolerated in SJSA cells, proliferation was reduced. Notably, proliferation defects were rescued upon the reexpression of wild-type or kinase-dead CDK19. Comparative RNA sequencing analyses showed reduced expression of mitotic genes and activation of genes associated with cholesterol metabolism and the p53 pathway in CDK19 knockdown cells. SJSA cells treated with 5-fluorouracil, which induces metabolic and genotoxic stress and activates p53, further implicated CDK19 in p53 target gene expression. To better probe the p53 response, SJSA cells (shCDK19 versus shCTRL) were treated with the p53 activator nutlin-3. Remarkably, CDK19 was required for SJSA cells to return to a proliferative state after nutlin-3 treatment, and this effect was kinase independent. These results implicate CDK19 as a regulator of p53 stress responses and suggest a role for CDK19 in cellular resistance to nutlin-3.

scholarly journals 2-Nitroimidazoles induce mitochondrial stress and ferroptosis in glioma stem cells residing in a hypoxic niche

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Naoyoshi Koike ◽  
Ryuichi Kota ◽  
Yoshiko Naito ◽  
Noriyo Hayakawa ◽  
Tomomi Matsuura ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stress Responses ◽  
Survival Benefit ◽  
Brain Slices ◽  
Glioma Stem Cells ◽  
Hypoxic Conditions ◽  
Significant Survival ◽  
Radiation Induced ◽  
Effects Of Radiation ◽  
Oxidative Stress Responses

AbstractUnder hypoxic conditions, nitroimidazoles can replace oxygen as electron acceptors, thereby enhancing the effects of radiation on malignant cells. These compounds also accumulate in hypoxic cells, where they can act as cytotoxins or imaging agents. However, whether these effects apply to cancer stem cells has not been sufficiently explored. Here we show that the 2-nitroimidazole doranidazole potentiates radiation-induced DNA damage in hypoxic glioma stem cells (GSCs) and confers a significant survival benefit in mice harboring GSC-derived tumors in radiotherapy settings. Furthermore, doranidazole and misonidazole, but not metronidazole, manifested radiation-independent cytotoxicity for hypoxic GSCs that was mediated by ferroptosis induced partially through blockade of mitochondrial complexes I and II and resultant metabolic alterations in oxidative stress responses. Doranidazole also limited the growth of GSC-derived subcutaneous tumors and that of tumors in orthotopic brain slices. Our results thus reveal the theranostic potential of 2-nitroimidazoles as ferroptosis inducers that enable targeting GSCs in their hypoxic niche.

Stimuli and consequences of dendritic release of oxytocin within the brain

2007 ◽  
Vol 35 (5) ◽  
pp. 1252-1257 ◽  
Author(s):  
I.D. Neumann
Keyword(s):  
Paraventricular Nucleus ◽  
Stress Responses ◽  
Supraoptic Nucleus ◽  
Brain Regions ◽  
Model System ◽  
Intracerebral Microdialysis ◽  
Psychotherapeutic Intervention ◽  
Psychiatric Illnesses ◽  
Oxytocin Release ◽  
The Brain

The brain oxytocin system has served as a distinguished model system in neuroendocrinology to study detailed mechanisms of intracerebral release, in particular of somatodendritic release, and its behavioural and neuroendocrine consequences. It has been shown that oxytocin is released within various brain regions, but evidence for dendritic release is limited to the main sites of oxytocin synthesis, i.e. the hypothalamic SON (supraoptic nucleus) and PVN (paraventricular nucleus). In the present paper, stimuli of dendritic release of oxytocin and the related neuropeptide vasopressin are discussed, including parturition and suckling, i.e. the period of a highly activated brain oxytocin system. Also, exposure to various pharmacological, psychological or physical stressors triggers dendritic oxytocin release, as monitored by intracerebral microdialysis within the SON and PVN during ongoing behavioural testing. So far, dendritic release of the neuropeptide has only been demonstrated within the hypothalamus, but intracerebral oxytocin release has also been found within the central amygdala and the septum in response to various stimuli including stressor exposure. Such a locally released oxytocin modulates physiological and behavioural reproductive functions, emotionality and hormonal stress responses, as it exerts, for example, pro-social, anxiolytic and antistress actions within restricted brain regions. These discoveries make oxytocin a promising neuromodulator of the brain for psychotherapeutic intervention and treatment of numerous psychiatric illnesses, for example, anxiety-related diseases, social phobia, autism and postpartum depression.

p53 and PPP1R13L (alias iASPP or RAI) form a feedback loop to regulate genotoxic stress responses

2010 ◽  
Vol 1800 (12) ◽  
pp. 1231-1240 ◽  
Author(s):  
Magdalena J. Laska ◽  
Ulla B. Vogel ◽  
Uffe B. Jensen ◽  
Bjørn A. Nexø
Keyword(s):  
Stress Responses ◽  
Feedback Loop ◽  
Genotoxic Stress

scholarly journals Protective Effect of Kit Signaling for Melanocyte Stem Cells against Radiation-Induced Genotoxic Stress

2011 ◽  
Vol 131 (9) ◽  
pp. 1906-1915 ◽  
Author(s):  
Hitomi Aoki ◽  
Akira Hara ◽  
Tsutomu Motohashi ◽  
Takahiro Kunisada
Keyword(s):  
Stem Cells ◽  
Protective Effect ◽  
Genotoxic Stress ◽  
Melanocyte Stem Cells ◽  
Radiation Induced

scholarly journals The Isolation of Antioxidant Enzymes from Mature Tomato (cv. Micro-Tom) Plants

HortScience ◽  
2008 ◽  
Vol 43 (5) ◽  
pp. 1608-1610 ◽  
Author(s):  
Priscila L. Gratão ◽  
Carolina C. Monteiro ◽  
Lázaro E.P. Peres ◽  
Ricardo Antunes Azevedo
Keyword(s):  
Oxidative Stress ◽  
Stress Responses ◽  
Gel Electrophoresis ◽  
Model System ◽  
Guaiacol Peroxidase ◽  
Abiotic And Biotic Stresses ◽  
Plant Model ◽  
Activity Staining ◽  
Biotic Stresses ◽  
Oxidative Stress Responses

The activity of catalase (CAT), guaiacol peroxidase (GPOX), ascorbate peroxidase (APX), glutathione reductase (GR), and the isoenzymes of superoxide dismutase (SOD) were determined in the organs of tomato (Lycopersicon esculentum) cultivar Micro-Tom after 104 days of development. The total activities of CAT, GPOX, and GR were higher in the stem than in others tissues, whereas the stem exhibited the lowest APX activity. Activity staining analysis following gel electrophoresis revealed the existence of four SOD isoenzymes in leaves, three in fruits, but only two in the roots and stems. This characterization is essential for an investigation into the effect of abiotic and biotic stresses on the oxidative stress responses by this plant model system.

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