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Lisse, T. S.

Publications and source records attributed to Lisse, T. S..

3 recordsLinked to original sources

Vitamin D regulation of a SOD1-to-SOD2 antioxidative switch to prevent osteosarcoma transformation

Superoxide, a form of reactive oxygen species (ROS), is catabolized by superoxide dismutase (SOD) and contributes to carcinogenesis via the oxidative damage it inflicts on cells. The aim of this research was to analyze the potential vitamin D-mediated regulation of the antioxidative "SOD1-to-SOD2 switch" within the human MG-63 osteosarcoma model. For this study, real-time PCR analysis was performed using MG-63 cells exposed to metabolically active 1,25(OH)2D3. Frist, a sustained statistically significant >2-fold suppression of proliferating cell nuclear antigen (PCNA) transcripts was observed after 10nM but not at 100nM of 1,25(OH)2D3 treatment, suggesting a cytostatic effect. In order to assess regulators of mitochondrial oxidative phosphorylation, gene expression of COX2 and COX4l1 of the mitochondrial complex IV and antioxidative enzymes (SOD1, SOD2 and Catalase (CAT)) were monitored. For COX2 and COX4l1, no changes in gene expression were observed. However, a concomitant decrease in CAT and SOD1 mRNA, and increase in SOD2 mRNA after 24 hours of 10nM 1,25(OH)2D3 treatment were observed. A ~8-fold increase in SOD2 mRNA was apparent after 48 hours. The significant increase in SOD2 activity in the presence of vitamin D indicates an antioxidant potential and sensitization of vitamin D during osteosarcoma transformation and mitochondrial detoxification over time.

cancer biology

Dicer- and BSC-dependent miRNAs during murine anagen development

MicroRNAs (miRNAs) are a major class of conserved non-coding RNAs that have a wide range of functions during development and disease. Biogenesis of canonical miRNAs depend on the cytoplasmic processing of pre-miRNAs to mature miRNAs by the Dicer endoribonuclease. Once mature miRNAs are generated, the miRNA-induced silencing complex, or miRISC, incorporates one strand of miRNAs as a template for recognizing complementary target messenger RNAs (mRNAs) to dictate post-transcriptional gene expression. Besides regulating miRNA biogenesis, Dicer is also part of miRISC to assist in activation of the complex. Dicer associates with other regulatory miRISC co-factors such as trans-activation responsive RNA-binding protein (Tarbp2) to regulate miRNA-based RNA interference. Although the functional role of miRNAs within epidermal keratinocytes have been extensively studied within embryonic and post-natal mouse skin, its contribution to the normal function of hair follicle bulge stem cells (BSCs) during post-natal hair follicle development is unknown. With this question in mind, we sought to ascertain whether Dicer-Tarpb2 plays a functional role within BSCs during induced anagen development by utilizing conditional knockout mouse models. Our findings suggest that Dicer, but not Tarbp2, functions within BSCs to regulate induced anagen (growth) development of post-natal hair follicles. These findings strengthen our understanding of miRNA-dependency within hair follicle cells to define a boundary for post-transcriptional gene regulation during anagen development.

molecular biology

Short-wavelength violet light (420nm) stimulates melanopsin-dependent acute alertness responses in zebrafish

Sunlight throughout the day and seasons strongly influences our biological rhythms and activity. In recent years, it has become evident that night-time overexposure to bright light in urban environments can profoundly affect physiology and behaviour in humans and animals. In particular, the artificial emission of short-wavelength light has been shown to stimulate alertness in humans, but the mechanisms remain largely unknown. Utilising a diurnal larval zebrafish model, we identified instant, non-image-forming (NIF) responses to short-wavelength violet light (~420nm), which are activated only during light exposure, and are reminiscent of alertness, including increased heart rate, enhanced locomotor activity, and pectoral fin beating (for increased oxygen supply). We further determined that these responses are driven by sympathetic neuronal circuits and depend on the zebrafish melanopsin homologue Opn4a. We also found that these responses can be modulated by the sleep-regulatory hormone melatonin, but that melatonin is not essential. Our findings reveal a previously unknown mechanism for violet light-dependent acute alertness.

animal behavior and cognition