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The mechanism by which ethane 1,2-dimethanesulfonate (EDS) selectively kills Leydig cells is poorly understood. To characterize further the cell-specific actions of EDS, we studied biochemical and morphological changes during apoptosis in different Leydig cell and non-steroidogenic cell models.Rat testicular and H540 tumor Leydig cells were killed by 1-2 mM EDS, whereas 20 mM EDS were required for MA-10 cells. This higher concentration of EDS was also necessary for activation of apoptosis in non-steroidogenic Chinese hamster ovary cells, whereas COS-1 monkey kidney cells were resistant. These variable effects of EDS on apoptosis were independent of new protein synthesis and, interestingly, could be delayed by co-incubation with dibutyrl cyclic AMP. Along with cell death, we also observed chromosomal fragmentation and other hallmarks indicative of apoptosis as evidenced by DNA laddering and fluorescent microscopy. Time-lapse photography with a confocal microscope showed that the time of onset, duration and even the sequence of apoptotic events between individual H540 cells was heterogeneous. When the dose of EDS was gradually increased from 2 to 10 mM, the proportion of cells showing normal apoptotic features gradually decreased. Intriguingly, treatment with 10 mM EDS did not result in death for most cells and was marked by an absence of DNA laddering and ultrastructural features of apoptosis and necrosis. However, incubation with 20 mM EDS resulted in necrosis.These results demonstrated that the effects of EDS on cell survival are not specific to Leydig cells, that different cell types have different sensitivities to EDS and that stimulation of the cAMP pathway may mitigate EDS action. The data obtained with H540 cells further revealed that EDS can induce two types of programmed cell death.
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Departments of, Child Health Care, General Surgery, Institute of Pediatric Research, Department of Public Health and Clinical Medicine, Nanjing Children's Hospital, Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, People's Republic of China
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evidence indicates that the early nutritional status of an organism may be a programming factor for the development of obesity and metabolic syndrome later in life ( Ong & Loos 2006 , Symonds et al . 2009 ), particularly malnutrition or overnutrition
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intestine and colon) tumorigenesis in male Sprague–Dawley rats, whose dams consumed soy protein isolate (SPI) or the major soy isoflavone GEN during pregnancy. We report novel associations of dietary SPI during pregnancy with long-lasting (programed) changes
Department of Biological Sciences, Stanford University, Stanford, California 94305-5020, USA
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Department of Biological Sciences, Stanford University, Stanford, California 94305-5020, USA
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Department of Biological Sciences, Stanford University, Stanford, California 94305-5020, USA
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fluorescent data (background subtracted data) provided by the MyIQ software (BioRad) were analyzed using the real-time PCR Miner program ( Zhao & Fernald 2005 ), which uses the resultant PCR efficiency and fractional cycle number of the threshold (CT) for gene
Department of Physiology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, Victoria, Australia
Prostate Cancer Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Cabrini Institute, Cabrini Health, Malvern, Victoria, Australia
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Prostate Cancer Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Cabrini Institute, Cabrini Health, Malvern, Victoria, Australia
Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, Victoria, Australia
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Prostate Cancer Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Cabrini Institute, Cabrini Health, Malvern, Victoria, Australia
Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, Victoria, Australia
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PDXs. These models are becoming critical to preclinical discovery and testing programs in Australia and overseas ( Lawrence et al. 2018 , 2021 , Watt et al. 2019 , Nyquist et al. 2020 , Porter et al. 2021 ). Towards development of more
Laboratory of Neurosciences, Department of Pathology, Biomolecular Science Center, Department of Pharmaceutical Sciences, Division of Life and Pharmaceutical Sciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland 21224, USA
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Laboratory of Neurosciences, Department of Pathology, Biomolecular Science Center, Department of Pharmaceutical Sciences, Division of Life and Pharmaceutical Sciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland 21224, USA
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not used immediately, it was kept at −20 °C until further analysis. Serum testosterone concentrations from individual mice were measured by National Hormone & Peptide Program Harbor-UCLA Medical Center, Torrance, CA, USA by RIA after ether extraction
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% confluency was reached in a fresh culture medium. Human islets were provided by the National Institute of Diabetes and Digestive and Kidney Diseases-funded Integrated Islet Distribution Program at the City of Hope. For primary cultures, human islets were
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Fred Hutchinson Cancer Research Center, Department of Epidemiology, Division of Metabolism, Department of Public Health Sciences, Cancer Prevention Program, 1100 Fairview Avenue N., Seattle, Washington 98109, USA
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Fred Hutchinson Cancer Research Center, Department of Epidemiology, Division of Metabolism, Department of Public Health Sciences, Cancer Prevention Program, 1100 Fairview Avenue N., Seattle, Washington 98109, USA
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Fred Hutchinson Cancer Research Center, Department of Epidemiology, Division of Metabolism, Department of Public Health Sciences, Cancer Prevention Program, 1100 Fairview Avenue N., Seattle, Washington 98109, USA
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Fred Hutchinson Cancer Research Center, Department of Epidemiology, Division of Metabolism, Department of Public Health Sciences, Cancer Prevention Program, 1100 Fairview Avenue N., Seattle, Washington 98109, USA
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Fred Hutchinson Cancer Research Center, Department of Epidemiology, Division of Metabolism, Department of Public Health Sciences, Cancer Prevention Program, 1100 Fairview Avenue N., Seattle, Washington 98109, USA
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Fred Hutchinson Cancer Research Center, Department of Epidemiology, Division of Metabolism, Department of Public Health Sciences, Cancer Prevention Program, 1100 Fairview Avenue N., Seattle, Washington 98109, USA
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(CPM-stimulated cells–CPM-unstimulated cells). A multi-factorial proliferation analysis of flow cytometry results was generated with the ModFit LT Program (Verity Software House LT, Topsham, ME, USA). Parameters of lymphocyte proliferation evaluated by
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Introduction: evidence for pregnancy adaptation of cell signaling and associated changes in nitric oxide output Pregnancy-specific programming of endothelial nitric oxide production Nitric oxide (NO) is an important vasodilator produced by vascular
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Insulin secretion and glucose tolerance were studied in 20-week-old male and female offspring of rat dams maintained on an isocaloric 20% or 8% protein diet during pregnancy and lactation after transfer to the same diet at weaning. Protein-restricted male and female offspring were also weaned onto a 20% protein diet. In males, post-absorptive insulin concentrations were suppressed by protein restriction from conception to adulthood (by 41%; P<0.001); however, basal insulin levels were 2.6-fold higher (P<0.001) if protein restriction was limited to gestation and lactation. Post-absorptive insulinaemia in females was unaffected by early or sustained protein restriction, but was lower than for males in the control group and the group exposed to protein restriction during early life alone (by 40% (P<0.001) and 52% (P<0.001) respectively). Plasma insulin/blood glucose ratios were higher in males compared with females in both control and early protein-restricted groups (1.6-fold (P<0.05) and 2.3-fold (P<0.001) respectively). A positive linear relationship existed between mean ambient insulin and glucose concentrations in males (r=1.0) and females (r=0.9), but the gradient was 12.4-fold greater (P<0.01) in males. beta-Cell function was evaluated after intravenous glucose challenge. In males, the acute insulin response and the suprabasal 30-min area under the insulin curve were dramatically higher in rats exposed to protein restriction during gestation and lactation alone (2.6- and 2.8-fold respectively; P<0.001). In contrast, these parameters were lowered by extending the exposure to protein restriction to adulthood in males, and by either early or prolonged exposure to protein restriction in females. The insulin resistance index was increased (2.5-fold; P<0.001) in male, but not female, rats exposed to protein restriction during gestation and lactation alone, and was not increased by extending the period of protein restriction to adulthood in either sex. Thus the data have demonstrated gender-specific lowering of insulin sensitivity due to protein restriction during early life only. The insulinogenic index (insulin response in relation to prevailing glycaemia) was increased in male, but not female, rats exposed to protein restriction during gestation and lactation alone (3.0-fold; P<0.001). A modest decline in insulin secretion in the female groups exposed to protein restriction until either the end of lactation or adulthood was compensated by increased insulin sensitivity, as demonstrated by significant decreases in the insulin resistance index in both groups (by 48% and 52% respectively; P<0.05). Glucose disappearance rates did not differ between the male and female control or early protein-restricted groups but were higher in both male (31%; P<0.05) and female groups (46%; P<0.001) exposed to protein restriction from conception to adulthood. Marked gender differences in glucose-stimulated insulin secretion were not associated with gender differences with respect to glucose tolerance. Our data therefore demonstrated that exposure to protein restriction during early life alone leads to relative insulin resistance and hyperinsulinaemia in adulthood, but this relationship is gender specific, observed only in males, and glucose tolerance is maintained.
