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Kaminska, J.

Publications and source records attributed to Kaminska, J..

3 recordsLinked to original sources

Radiation-induced disruption of cardiac mitochondrial bioenergetics and nucleotide homeostasis in mice

AimsCardiac stereotactic body radiotherapy (SBRT) has emerged as a promising non-invasive treatment for refractory ventricular tachycardia (VT). Intriguingly, the clinical benefit of SBRT often occurs within days of treatment, preceding the development of radiation-induced fibrosis, suggesting alternative underlying mechanisms. This study aimed to investigate the acute and persistent effects of ionizing radiation on cardiac bioenergetics and mitochondrial function, providing mechanistic insights into early cardiac responses to radiation exposure. Methods and resultsWe employed a translational multi-model approach, including HL-1 mouse cardiomyocytes and ex vivo mouse left ventricular living myocardial slices (LMS). Bioenergetic profiling, assessment of mitochondrial respiration and calcium handling were performed following exposure to clinically relevant radiation doses (10 Gy and 25 Gy). In HL-1 cardiomyocytes, 10 Gy induced acute bioenergetic stress, characterized by reduced adenylate energy charge, cytoskeletal disorganization, and impaired mitochondrial respiration, accompanied by increased calcium oscillation amplitude. 25 Gy exposure led to NAD+ depletion but paradoxically enhanced mitochondrial respiratory capacity, suggesting an adaptive metabolic response. Murine myocardial slices demonstrated reduced creatine content while preserving energy balance as indicated by phosphocreatine/ATP ratio, indicating tissue-level metabolic resilience. These findings reveal model-specific metabolic perturbations induced by cardiac irradiation, underscoring the importance of tissue complexity in modulating the cardiac response to radiation. ConclusionThis study demonstrates that ionizing radiation at 10 Gy and 25 Gy induced dose- and model-dependent bioenergetic alterations in cardiac cells and tissues, including changes in mitochondrial respiration, nucleotide levels, and redox balance. While 10 Gy exacerbated metabolic disruption, 25 Gy triggered partial recovery, highlighting differential responses across cellular and tissue levels. These metabolic changes may contribute to the immediate effects of cardiac SBRT and potentially to long-term cardiotoxicity. Translational PerspectiveOur study provides novel mechanistic insights into the metabolic effects of cardiac irradiation, revealing acute mitochondrial stress, redox imbalance and alterations in calcium homeostasis in cardiomyocytes. These early bioenergetic changes may contribute to both the immediate anti-arrhythmic effects and the potential long-term cardiotoxicity of stereotactic body radiation therapy. Understanding these molecular responses is essential to optimize the therapeutic window of cardiac radioablation and minimize adverse effects. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/730816v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@10b34bcorg.highwire.dtl.DTLVardef@b34a28org.highwire.dtl.DTLVardef@c995c9org.highwire.dtl.DTLVardef@88f8f8_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

Visual perception and workload of office workers in various acoustic conditions

Noise in the office work environment can negatively affect workers cognitive performance, number of errors made and comfort. The aim of the study was to determine the effects of various types of acoustic conditions in the mental work environment on visual perception (eye-tracking parameters) and workload. Method: In the experiment a group of 39 people aged 20 to 34 was asked to perform two eye-tracking tests (Perceptiveness and Speed Tests (PTs) and to read the text of a fictional biography, and then to answer questions about the reading). Mental workload was evaluated in each condition using NASA TLX questionnaire. The tests were performed in various acoustic conditions: variant W1 - no presentation of acoustic stimuli, variant W2 - sounds of office equipment, variant W3 - sounds of office equipment with quiet conversation in native language, variant W4 - sounds of office equipment with loud conversation in native language, variant W5 - filtered pink noise. In variants from W2 to W5 the equivalent sound level A was 55 dB. Results: The assessment of work efficiency in the reading test indicates the existence of statistically significant differences. The most errors were made during mental work with the audible sounds of office equipment with a loud conversation (Variant W4) and during mental work performed with audible filtered pink noise (W5). While reading the text, different acoustic conditions do not differentiate statistically significantly visual perception described by eye-tracking parameters. In turn, in the PTs test, statistically significant differences between the variants were found in the Digit test (average blink duration) and the Fraction test (average blink duration, average fixation duration and saccades frequency parameters). In conclusion, visual perception depends on the type of noise. Acoustic factors aggect workers cognitive functions, mostly in more difficult tasks.

bioengineering↗

Intracellular level of S. cerevisiae Rad51 is regulated via proteolysis in a SUMO- and Ubiquitin-dependent manner

Among various DNA lesions, the DNA double-strand breaks are particularly deleterious; especially, when an error-free repair pathway is unavailable, and the cell takes the risk of using the error-prone recombination pathways to repair the DNA breaks, resume the cell cycle, and continue growth. The latter comes at the expense of decreased well-being of the cells due to genome rearrangements. One of the major players involved in recombinational repair of DNA damage is Rad51 recombinase, a protein responsible for presynaptic complex formation. We previously noticed that the level of this protein is strongly increased when illegitimate recombination is engaged in repair. The regulation of Rad51 protein turnover is not known; therefore, we decided to look closer at this issue because we expect that an excessively high level of Rad51 may lead to genome instability. Here we show that the level of Rad51 is regulated via the ubiquitin-dependent proteolytic pathway. The ubiquitination of Rad51 depends on multiple E3 enzymes, including SUMO-targeted ubiquitin ligases. We also demonstrate that Rad51 can be modified by both ubiquitin and SUMO. Moreover, these modifications may lead to opposite effects. Ubiquitin-dependent degradation depends on Rad6, Rad18, Slx8, Dia2 and the anaphase-promoting complex. Rsp5-dependent ubiquitination leads to Rad51 stabilization.

genetics↗