Biology subjects

Reisz, J.

Publications and source records attributed to Reisz, J..

3 recordsLinked to original sources

bioRxiv2025

Incorporation of microbially salvaged urea-nitrogen into anabolic amino acids during hibernation in arctic ground squirrels

Hibernators rely on endogenous supplies of amino acids (AAs) and other nutrients to sustain organ function and skeletal muscle mass. Gut microbiota-mediated recycling of urea-nitrogen into AAs has long been considered a mechanism to assist in conserving nitrogen; however, the relevance of urea nitrogen salvage (UNS) to overall host physiology and metabolism is debated. We hypothesized that incorporation of microbially-liberated urea-nitrogen (MLUN) into AAs would be higher in host tissues of hibernating arctic ground squirrels compared to those of summer active squirrels, and that MLUN would support synthesis of anabolic AAs that regulate protein balance. To test this, we injected [13C, 15N2]-urea into summer squirrels and into squirrels hibernating at an ecologically relevant ambient temperature (-16{degrees}C). We found greater incorporation of MLUN into non-essential AAs and specific essential AAs in several tissues of hibernating squirrels compared to summer. We also observed increased 15N enrichment in leucine-isoleucine, citrulline and glutamine, anabolic AAs known to influence protein balance and trans-organ nitrogen balance. Compared to studies in which ground squirrels hibernated at ambient temperatures above 0{degrees}C, our results suggest that squirrels hibernating at subzero temperatures may up modulate synthesis of AAs that preserve protein and nitrogen balance during prolonged fasting and inactivity.

systems biology↗

bioRxiv2023

Toxins in plastic: Evidence for the cardiodepressive effects of di-2-ethylhexylphthalate (DEHP)

Di-2-ethylhexylphthalate (DEHP) is commonly used in the manufacturing of plastic materials, including intravenous bags, blood storage bags, and medical-grade tubing. DEHP can leach from plastic medical products, which can result in inadvertent patient exposure. DEHP concentrations were measured in red blood cell (RBC) units stored between 7-42 days (23-119 g/mL). Using these concentrations as a guide, Langendorff-perfused rat heart preparations were acutely exposed to DEHP. Sinus activity remained stable with lower doses of DEHP (25-50 g/mL), but sinus rate declined by 43% and sinus node recovery time prolonged by 56.5% following 30-minute exposure to 100 g/ml DEHP. DEHP exposure also exerted a negative dromotropic response, as indicated by a 69.4% longer PR interval, 108.5% longer Wenckebach cycle length, and increased incidence of atrioventricular uncoupling. Pretreatment with doxycycline partially rescued the effects of DEHP on sinus activity, but did not ameliorate the effects on atrioventricular conduction. DEHP exposure also prolonged the ventricular action potential and effective refractory period, but had no measurable effect on intracellular calcium transient duration. Follow-up studies using hiPSC-CM confirmed that DEHP slows electrical conduction in a time (15 min - 3 hours) and dose-dependent manner (10-100 g/mL). Previous studies have suggested that phthalate toxicity is specifically attributed to metabolites of DEHP, including mono-2-ethylhexyl phthalate (MEHP). This study demonstrates that DEHP exposure also contributes to cardiac dysfunction in a dose- and time-dependent manner. Future work is warranted to investigate the impact of DEHP (and its metabolites) on human health, with special consideration for clinical procedures that employ plastic materials.

pharmacology and toxicology↗

bioRxiv2021

Cytoplasmic labile iron accumulates in aging stem cells perturbing a key rheostat for identity control

Bone marrow resident and rarely dividing haematopoietic stem cells (HSC) harbour an extensive self-renewal capacity to sustain life-long blood formation;1-5 albeit their function declines during ageing.6, 7 Various molecular mechanisms confer stem cell identity, ensure long-term maintenance and are known to be deregulated in aged stem cells.8, 9 How these programs are coordinated, particularly during cell division, and what triggers their ageing-associated dysfunction has been unknown. Here, we demonstrate that HSC, containing the lowest amount of cytoplasmic chelatable iron (labile iron pool)10 among hematopoietic cells, activate a limited iron response during mitosis. Engagement of this iron homeostasis pathway elicits mobilization and {beta}-oxidation of arachidonic acid and enhances stem cell-defining transcriptional programs governed by histone acetyl transferase Tip60/KAT5. We further find an age-associated expansion of the labile iron pool, along with loss of Tip60/KAT5-dependent gene regulation to contribute to the functional decline of ageing HSC, which can be mitigated by iron chelation. Together, our work reveals cytoplasmic redox active iron as a novel rheostat in adult stem cells; it demonstrates a role for the intracellular labile iron pool in coordinating a cascade of molecular events which reinforces HSC identity during cell division and to drive stem cell ageing when perturbed. As loss of iron homeostasis is commonly observed in the elderly, we anticipate these findings to trigger further studies into understanding and therapeutic mitigation of labile iron pool-dependent stem cell dysfunction in a wide range of degenerative and malignant pathologies.

cell biology↗