Dong Kun Lee

Spaceflight exposes astronauts to multiple environmental stressors that promote oxidative stress, including ionizing radiation, microgravity, circadian rhythm disruption, and psychological stress. These factors increase the production of reactive oxygen species (ROS) and disturb redox homeostasis, potentially affecting multiple physiological systems during long-duration missions. In addition to environmental challenges, nutritional factors may further influence oxidative balance in space. Space food systems rely on long-term storage and processing, which can lead to degradation of antioxidant nutrients and alterations in dietary composition. Furthermore, spaceflight conditions may modify eating behaviors and disrupt gut microbiome composition, both of which are closely linked to host redox regulation. This review examines current knowledge on oxidative stress during spaceflight and discusses how space food systems, dietary composition, and microbiome alterations interact with spaceflight stressors to influence redox homeostasis. Potential strategies to mitigate oxidative stress are also discussed, including preservation of antioxidant nutrients, optimization of dietary composition, reduction in pro-oxidant exposures, and microbiome-targeted approaches to support astronaut health during long-duration missions.

Pro-opiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC) play a pivotal role in regulating brown adipose tissue (BAT) thermogenesis via the sympathetic nervous system. The activation of transient receptor potential ankyrin 1 (TRPA1) has been demonstrated to enhance heat production, particularly in BAT. However, no direct evidence has been reported regarding BAT thermogenesis mediated by TRPA1-regulated ARC POMC neurons. This study aimed to investigate the role of TRPA1-expressing hypothalamic POMC neurons in BAT thermogenesis. To confirm TRPA1 expression in ARC POMC neurons, we employed single-cell reverse transcriptase polymerase chain reaction and immunolabeling techniques. Selective TRPA1 agonists, including capsiate and ASP7663, induced depolarization of ARC POMC neurons, an effect that was inhibited by A967079, a TRPA1-selective antagonist. Furthermore, intracerebroventricular (i.c.v.) administration of ASP7663 increased BAT and core body temperature. The thermogenic effect of ASP7663 in BAT was abolished by co-administration of A967079. Among the BAT thermogenic markers, peroxisome proliferator-activated receptor gamma coactivator 1-alpha and PR domain containing 16 (PRDM16) expressions were considerably upregulated following i.c.v. administration of ASP7663. However, this increase was reversed by A967079, except for PRDM16. These findings indicate that TRPA1-mediated activation of hypothalamic POMC neurons is critical in regulating BAT thermogenesis and promoting energy expenditure.

The major function of primary order neurons in the arcuate nucleus of the hypothalamus is control of energy homeostasis. Among these neurons, proopiomelanocortin (POMC) neurons play a significant role in controlling anorexigenic feeding behavior and upregulating energy expenditure. In addition, transient receptor potential melastatin 2 (TRPM2) is a well-established temperature sensor, but no evidence of regulation of brown adipose tissue (BAT) thermogenesis via POMC^TRPM2 neurons in the arcuate nucleus has been reported so far. Here, through single-cell reverse-transcription and immunohistochemistry analyses, we confirmed that a subset of POMC neurons express TRPM2. Also, we confirmed the neuronal connection between POMC and BAT using cholera toxin subunit B. The chemogenetic stimulation of POMC neurons induced BAT thermogenesis, and this thermogenic effect was inhibited by a TRPM2 blocker. These results indicate that TRPM2 could modulate POMC neuronal activity and play a role in regulating BAT activity through neuronal connections. Adenosine diphosphoribose (ADPR), a TRPM2 agonist, depolarized POMC neurons, and this effect was suppressed by TRP and TRPM2 antagonists. In addition, intracerebrovascular injection of ADPR increased c-Fos expression of a subset of POMC neurons, BAT and core body temperature and expression of IRF-4, but not uncoupling protein 1, in normal chow diet- and high-fat diet-fed mice. TRPM2 antagonists blocked this increase. Our findings offer new insights into the physiological mechanism of IRF-4-mediated BAT thermogenesis, which is regulated by acute activation of hypothalamic POMC^TRPM2 neurons. Consequently, these approaches to promoting BAT thermogenesis can provide novel basic concepts to establish therapeutic strategies and precautions to combat metabolic disorders.

Background/Objectives: Platelet-derived growth factor receptor alpha (PDGFRα) is a receptor involved in cell growth and differentiation, with unclear roles in ovarian tissues and potential interactions with KCNK3 (potassium two-pore domain channel subfamily K member 3), a member of the two-pore domain K⁺ channel involved in cellular homeostasis. This study aims to map PDGFRα expression across mouse tissues and to explore its co-expression with KCNK3 in the ovary. Methods: We visualized PDGFRα expression using RNA-seq data from the genotype-tissue expression (GTEx) BodyMAP across 54 human tissues and Cap Analysis of Gene Expression (CAGE) data for various mouse tissues. In PDGFRα^EGFP mice expressing EGFP in PDGFRα⁺ cells, histological and fluorescence imaging were used to assess ovarian expression. Immunohistochemistry determined the co-localization of PDGFRα and KCNK3, and qPCR quantified their mRNA levels in the ovary, oviduct, and uterus. Results: PDGFRα showed high expression in human and mouse female reproductive tissues, particularly the ovary. In the PDGFRα^EGFP mouse model, PDGFRα was primarily found in the thecal layer and stromal cells, not in granulosa cells or oocytes. Immunohistochemistry indicated that 90.2 ± 8.7% of PDGFRα⁺ cells expressed KCNK3 in the ovarian stroma. qPCR revealed lower PDGFRα and KCNK3 expression in the ovary compared to the oviduct and uterus. Conclusions: This study shows that PDGFRα is predominantly expressed in ovarian stromal and theca cells and is highly co-localized with KCNK3, suggesting a potential role for PDGFRα⁺ cells in ionic regulation and their possible involvement in follicular development and ovarian physiology.

Background/Objectives: Platelet-derived growth factor receptor alpha (PDGFRα) is a receptor involved in cell growth and differentiation, with unclear roles in ovarian tissues and potential interactions with potassium two pore domain channel subfamily K member 3 (KCNK3). This study aims to map PDGFRα expression across mouse tissues and to explore its co-expression with KCNK3 in the ovary. Methods: We visualized PDGFRα expression using RNA-seq data from the genotype-tissue expression (GTEx) BodyMAP across 54 human tissues and cap analysis of gene expression (CAGE) data for various mouse tissues. In PDGFRαEGFP mice expressing EGFP in PDGFRα+ cells, histological and fluorescence imaging were used to assess ovarian expression. Immunohistochemistry determined the co-localization of PDGFRα and KCNK3, and qPCR quantified their mRNA levels in the ovary, oviduct, and uterus. Results: PDGFRα showed high expression in human and mouse female reproductive tissues, particularly the ovary. In the PDGFRαEGFP mouse model, PDGFRα was primarily found in the thecal layer and stromal cells, not in granulosa cells or oocytes. Immunohistochemistry indicated that 90.2 ± 8.7% of PDGFRα+ cells also expressed KCNK3 in the ovarian stroma. qPCR revealed lower PDGFRα and KCNK3 expression in the ovary compared to the oviduct and uterus. Conclusions: This study shows that PDGFRα is predominantly expressed in ovarian stromal and theca cells and is highly co-localized with KCNK3, implying a novel role for PDGFRα+ cells in maintaining ionic balance and potentially influencing follicular development and ovarian physiology.

Ovarian cysts are linked to hormone imbalances and altered gene expressions, but the connection between cysts and ion channel expression is understudied. This study explored the role of TWIK-related acid-sensitive K⁺ (TASK) channels in bovine ovarian cyst formation. The ovarian follicles were split into small (5 to 10 mm in diameter) and large (>25 mm in diameter) groups. Among the measured K⁺, Na⁺, and Cl⁻ concentrations in follicular fluid (FF) obtained from small-sized follicles (SFs) and large-sized follicles (LFs), the K⁺ concentration was significantly lower in LFFF. Quantitative PCR, Western blot, and immunocytochemistry data revealed that TASK-3 expression levels significantly decreased by approximately 50% in LFs and granulosa cells obtained from LFs (LFGCs) compared to the corresponding controls. The TASK-3 protein was localized to the plasma membranes of GCs. The diameters of LFGCs were larger than those of SFGCs. The cell swelling response to exposure to a hypotonic solution (200 mOsm/L) was highly reduced in TASK-3-overexpressing cells compared to vector-transfected cells. TASK-3-knockdown cells showed arrested growth. Senescence markers were detected in LFGCs and TASK-3-knockdown cells. These findings suggest that reduced TASK-3 expression in LFs is associated with the inhibition of GC growth, leading to senescence and cyst formation.

Min Seok Woo, Eun-Jin Kim, Dong Kun Lee, Chung Eun Lee, Eun-A Ko and Dawon Kang. Journal of Animal Reproduction and Biotechnology 2024;39:81-7. https://doi.org/10.12750/JARB.39.2.81

Spinach (Spinacia oleracea) is one of the most famous vegetables worldwide, rich in essential metabolites for various health benefits. It is a valuable plant source that has the potential to be a nutraceutical. This study aimed to evaluate the single characteristic marker compound to establish the validation of HPLC-DAD methods applied to the development of a nutraceutical using spinach samples. Six metabolites (1–6) were identified from the spinach samples such as freeze-dried spinach (FDS) and spinach extract concentrate (SEC) by LC-Q-TOF/MS analysis. Among the six metabolites, 3′,4′,5-trihydroxy-3-methoxy-6,7-methylenedioxyflavone 4′-glucuronide (TMG) was selected as a marker compound due to its highest abundance and high selectivity. The specificity, accuracy, linearity, precision, repeatability, limit of detection (LOD), and limit of quantification (LOQ) of TMG in the spinach samples (FDS and SEC) were validated according to AOAC international guideline. The specificity was confirmed by monitoring the well separation of the marker compound from other compounds of spinach samples in the base peak intensity (BPI) and ultraviolet (UV) chromatogram. The calibration curve of TMG (15.625~500 μg/mL) had reasonable linearity (R² = 0.999) considered with LOD and LOQ values, respectively. Recovery rate of TMG was 93–101% for FDS and 90–95% for SEC. The precision was less than 3 and 6% in the intraday and interday. As a result, the HPLC-DAD validation method of TMG in the spinach samples (FDS and SEC) was first established with AOAC and KFDA regulations for approving functional ingredients in functional foods.

Viruses have evolved sophisticated mechanisms to manipulate host cell processes and utilize intracellular organelles to facilitate their replication. These complex interactions between viruses and cellular organelles allow them to hijack the cellular machinery and impair homeostasis. Moreover, viral infection alters the cell membrane’s structure and composition and induces vesicle formation to facilitate intracellular trafficking of viral components. However, the research focus has predominantly been on the immune response elicited by viruses, often overlooking the significant alterations that viruses induce in cellular organelles. Gaining a deeper understanding of these virus-induced cellular changes is crucial for elucidating the full life cycle of viruses and developing potent antiviral therapies. Exploring virus-induced cellular changes could substantially improve our understanding of viral infection mechanisms.

Ovarian cysts are linked to hormone imbalances and altered gene expressions, but the connection between cysts and ion channel expression is understudied. This study explored the role of TWIK-related acid-sensitive K+ (TASK) channels in bovine ovarian cyst formation. The ovarian follicles were split into small (5 to 10 mm in diameter) and large (> 25 mm in diameter) groups. Among the measured K+, Na+, and Cl- concentrations in follicular fluid (FF) obtained from small-sized follicles (SF) and large-sized follicles (LF), the K+ concentration was significantly lower in LFFF. Quantitative PCR, western blot, and immunocytochemistry data revealed that TASK-3 expression levels significantly decreased by approximately 50% in both LF and granulosa cells obtained from LF (LFGCs) compared to the corresponding controls. The TASK-3 protein was localized to the plasma membrane of GCs. The diameter of LFGCs was larger than that of SFGC. The cell swelling response to exposure to a hypotonic solution (200 mOsm/L) was highly reduced in TASK-3-overexpressing cells compared to vector-transfected cells. TASK-3-knockdown cells showed arrested growth. Senescence markers were detected in LFGCs and TASK-3-knockdown cells. These findings suggest that reduced TASK-3 expression in LF is associated with the inhibition of GC growth, leading to senescence and cyst formation.