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Biology subjects

Gabor, C.

Publications and source records attributed to Gabor, C..

3 recordsLinked to original sources

Endothelial Cu Uptake Transporter CTR1 Senses Disturbed Flow to Promote Atherosclerosis through Cuproptosis

Endothelial cells (ECs) lining blood vessels sense disturbed blood flow (D-flow), which drives mitochondrial dysfunction and atherosclerosis. Copper (Cu) is an essential micronutrient, and its disruption of homeostasis has been implicated in atherosclerosis. Cellular Cu levels are tightly controlled by Cu transport proteins including the Cu importer CTR1. Cuproptosis is a recently discovered form of regulated cell death triggered by mitochondrial Cu accumulation, but its endogenous stimulants and role in atherosclerosis remain unknown. Using EC-specific CTR1-deficient mice and cultured ECs, we show that endothelial CTR1 responds to D-flow by increasing mitochondrial Cu levels through its interaction with the mitochondrial Cu transporter SLC25A3 at caveolae/lipid rafts. This leads to the aggregation of lipoylated mitochondrial proteins, mitochondrial dysfunction, and cuproptosis, thereby exacerbating atherosclerosis. Importantly, mitochondria-targeted Cu-chelating nanoparticles effectively mitigate D-flow-induced cuproptosis and atherosclerosis, highlighting the endothelial CTR1-SLC25A3-mitochondrial Cu axis as a potential therapeutic target.

cell biology↗

Ionizing radiation has negligible effects on the age, telomere length, and corticosterone levels of Chornobyl tree frogs

Pollutants, such as ionizing radiation, released at high levels by human activities can shape ecological and evolutionary processes. The accident occurred at Chornobyl nuclear power plant (Ukraine, April 1986) contaminated a large extension of territory after the deposition of radioactive material. Beyond the immediate negative impact caused by the accident, it is still under debate whether the chronic exposure to the radiation levels currently present in the area signifies a serious threat for organisms. One hypothesis suggests that current levels of radiation may cause unobservable damage in the short-term, but have long-term effects such as decreases in longevity. Here, we investigate through a field-based approach, whether current levels of radiation in Chornobyl negatively impact the age of a semi-aquatic vertebrate, the Eastern tree frog Hyla orientalis. We also explore whether radiation induces changes in an ageing marker, telomere length, or in the stress hormone corticosterone. We found no effect of total individual absorbed radiation (including both external and internal exposure) on frog age (n = 197 individuals sampled in three consecutive years). We also did not find any relationship between individual absorbed radiation and telomere length, but a negative relationship between individual absorbed radiation and corticosterone levels. Our results suggest that radiation levels currently experienced by tree frogs in Chornobyl may not be high enough to cause severe chronic damage to semi-aquatic vertebrates such as this species. This is the first study addressing age and stress hormones in Chornobyl wildlife, and thus future research will confirm if these results can be extended to other taxa.

ecology↗

Are the adverse effects of stressors on amphibians mediated by their effects on stress hormones?

Adverse effects of anthropogenic changes on biodiversity might be mediated by their impacts on the stress response of organisms. To test this hypothesis we crossed exposure to metyrapone, a synthesis inhibitor of the stress hormone corticosterone, with exposure to the herbicide atrazine and the fungal pathogen Batrachochytrium dendrobatidis (Bd) to assess whether the effects of these stressors on tadpoles and post-metamorphic frogs were mediated by corticosterone. Metyrapone countered atrazine-and Bd-induced corticosterone elevations. However, atrazine-and Bd-induced reductions in body size were not mediated by corticosterone because they persisted despite metyrapone exposure. Atrazine lowered Bd abundance without metyrapone but increased Bd abundance with metyrapone for tadpoles and frogs. In contrast, atrazine reduced tolerance of Bd infections because frogs exposed to atrazine as tadpoles had reduced growth with Bd compared to solvent controls; this effect was not countered by metyrapone. Our results suggest that the adverse effects of atrazine and Bd on amphibian growth, development, and tolerance of infection are not mediated primarily by corticosterone. Instead, these effects are likely a function of energy lost from atrazine detoxification, defense against Bd, or repair from damage caused by atrazine and Bd. Additional studies are needed to evaluate how often the effects of anthropogenic stressors are mediated by stress hormones.

ecology↗