• The Korean Journal of Physiology and Pharmacology
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• v.28 no.3
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• pp.183-196
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• 2024

Ferroptosis is a novel mechanism of programmed cell death, characterized by intracellular iron overload, intensified lipid peroxidation, and abnormal accumulation of reactive oxygen species, which ultimately resulting in cell membrane impairment and demise. Research has revealed that cancer cells exhibit a greater demand for iron compared to normal cells, indicating a potential susceptibility of cancer cells to ferroptosis. Stomach and colorectal cancers are common gastrointestinal malignancies, and their elevated occurrence and mortality rates render them a global health concern. Despite significant advancements in medical treatments, certain unfavorable consequences and drug resistance persist. Consequently, directing attention towards the phenomenon of ferroptosis in gastric and colorectal cancers holds promise for enhancing therapeutic efficacy. This review aims to elucidate the intricate cellular metabolism associated with ferroptosis, encompassing lipid and amino acid metabolism, as well as iron metabolic processes. Furthermore, the significance of ferroptosis in the context of gastric and colorectal cancer is thoroughly examined and discussed.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.159-164
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• 2023

Ferroptosis is a type of regulated cell death recently discovered, characterized by the accumulation of iron-dependent lipid peroxides in the cell membrane, and it involves a complex network of signaling pathways, including iron metabolism, lipid peroxidation, and redox regulation. The dysregulation of these pathways can lead to the induction of ferroptosis and the development of liver diseases, such as alcoholic liver disease, non-alcoholic fatty liver disease, viral hepatitis, and liver cancer. Studies have demonstrated that targeting key molecules involved in iron metabolism, lipid peroxidation, and redox regulation can reduce liver injury and improve liver function in different liver diseases by inhibiting ferroptosis. Thus, modulation of ferroptosis presents a promising therapeutic target for treating liver diseases. However, further research is required to gain a more comprehensive understanding of the mechanisms underlying the role of ferroptosis in liver diseases and to develop more effective and targeted treatments.

• IMMUNE NETWORK
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• v.24 no.3
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• pp.26.1-26.19
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• 2024

Recent advancements in various technologies have shed light on the critical role of metabolism in immune cells, paving the way for innovative disease treatment strategies through immunometabolism modulation. This review emphasizes the glucose metabolism of myeloid-derived suppressor cells (MDSCs), an emerging pivotal immunosuppressive factor especially within the tumor microenvironment. MDSCs, an immature and heterogeneous myeloid cell population, act as a double-edged sword by exacerbating tumors or mitigating inflammatory diseases through their immune-suppressive functions. Numerous recent studies have centered on glycolysis of MDSC, investigating the regulation of altered glycolytic pathways to manage diseases. However, the specific changes in MDSC glycolysis and their exact functions continue to be areas of ongoing discussion yet. In this paper, we review a range of current findings, including the latest research on the alteration of glycolysis in MDSCs, the consequential functional alterations in these cells, and the outcomes of attempts to modulate MDSC functions by regulating glycolysis. Ultimately, we will provide insights into whether these research efforts could be translated into clinical applications.

• Toxicological Research
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• v.11 no.1
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• pp.1-8
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• 1995

Fumonisins are a family of mycotoxins produced by the fungus Fusarium moniliforme which is a common contaminant in corn. Fumonisins are potent inhibitors of sphingosine and sphinganine N-acyltransferase (ceramide synthase), key enzymes in sphingolipid metabolism. The purpose of this study was to provide the evidence that the elevated levels of free sphingoid bases (primarily sphinganine) and depletion of complex sphingolipids were closely related to the inhibition of cell growth in LLC-$PK_1$ cells exposed to fumonisin $B_1$$(\leq 35 {\mu}M)$. Concentrations of fumonisin $B_1$ between 10 and $35 {\mu}M$ were known to inhibit cell growth without cytotoxicity in $LLC-PK_1$ cells (Yoo et al. Toxicol. Appl. Pharmacol. 114, 9-15, 1992). Cells exposed to 35$\mu M$ fumonisin B$_1$ for 48 and 72 hr developed a fibroblast-like (elongated and spindle-shaped) appearance and were less confluent than normal cells. At between 24 and 48 hr after exposure to fumonisin $B_1$ cells were beginning to show the inhibition of cell growth and at 72 hr the number of viable cells in fumonisin-treated cultures was about 50% of concurrent control cultures. During the 24 hr lag period preceding inhibition of cell growth, the free sphinganine levels in cells exposed to $35 {\mu}M$ fumonisin $B_1$ were highly elevated (approximately 230 fold higher than normal cells). The elevated levels of free sphinganine were $435\pm14$$pmoles/{10^6}$ cells at 48 hr and approximately TEX>$333\pm11$$pmoles/{10^6}$ cells in cells exposed to $35{\mu}M$ fumonisin$B_1$ at 72 hr, while the levels of free sphinganine in normal cells were less than 2$pmoles/{10^6}$ cells. Under the same condition, depletion of intracellular complex sphingolipids as a consequence of fumonisin inhibition of de novo sphingolipid biosynthesis and turnover pathway was appeared. Content of free sphingold bases in dividing cells was more elevated than in confluent cells at 24-48 hr after cells were exposed to $20{\mu}M$ fumonisin $B_1$. The dividing cells were showing the inhibition of cell growth at 48-72 hr and $20{\mu}M$ fumonisin $B_1$. The results of this study support the hypothesis that the inhibition of cell growth is very well related to the disruption of sphingolipid metabolism in $LLC-PK_1$ cells.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.06a
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• pp.126-126
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• 2017

Mitochondria are important in wheat, as in all crops, as the main source of ATP for cell maintenance and growth including vitamin synthesis, amino acid metabolism and photorespiration. To investigate the mitochondrial proteome of the roots of wheat seedlings, a systematic and targeted analysis were carried out on the mitochondrial proteome from 15 day-old wheat seedling root material. Mitochondria were isolated by Percoll gradient centrifugation; and extracted proteins were separated and analyzed by Tricine SDS-PAGE along with LTQ-FTICR mass spectrometry. From the isolated the sample, 184 proteins were identified which is composed of 140 proteins as mitochondria and 44 proteins as other subcellular proteins that are predicted by the freeware subcellular predictor. The identified proteins in mitochondria were functionally classified into 12 classes using the ProtFun 2.2 server based on biological processes. Proteins were shown to be involved in amino acid biosynthesis (17.1%), biosynthesis of cofactors (6.4%), cell envelope (11.4%), central intermediary metabolism (10%), energy metabolism (20%), fatty acid metabolism (0.7%), purines and pyrimidines (5.7%), regulatory functions (0.7%), replication and transcription (1.4%), translation (22.1%), transport and binding (1.4%), and unknown (2.8%). These results indicate that many of the protein components present and functions of identifying proteins are common to other profiles of mitochondrial proteins performed to date. This dataset provides the first extensive picture, to our knowledge, of mitochondrial proteins from wheat roots. Future research is required on quantitative analysis of the wheat mitochondrial proteomes at the spatial and developmental level.

• Korean Journal of Microbiology
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• v.6 no.2
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• pp.41-53
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• 1968

Studies on the carbohydrate metabolism of yeast as influenced by gamma-irradiation from cobalt-60 have been carried, then the mechanisms of radiation effect on respiration and fermentation were discussed under considerations of permeable changes of irradiated cell membrane. The cells of baker's yeast (Saccharomyces cerevisiae) which had been gamma-irradiated of 240 k.r. doses for an hour, then were put into aerobic oxidation and anaerobic fermentation without substrate. Total and fractionated carbohydrates of irradiated yeast cells were determined by calorimetric method with anthrone and orcinol reagents, the amounts of total carbohydrate, trehalose, RNA-ribose, PCA-soluble glycogen, alkali-soluble glycogen, acetic acid-soluble glycogen, mannan and glucan were determined according to the course of aerobic oxidation and anaerobic fermentation. It is found that the carbohydrates of irradiated cells leak out and amount of the losses teaches eleven times more than that of control, the volume of losses are seems to be replaced by water, it can be suggested the damage of gamma-irradiation occurs in the site of passive transport of cell membrane. The endogeneous aerobic respiration of irradiated cells are increased much more than control, the synthesis of reserve glycogen, glucan and RNA-ribose promoted much more than control. The anaerobic fermentation of irradiated cells are also increased than that of control, but the breakdown of carbohydrate is less than endogeneous respiration of irradiated cells. The synthetic rate is also less than that of aerobic oxidation. In irradiated yeast cells, trehalose is revealed to be primary substrate for endogeneous carbohydrate metabolism, so it is proved that the enzymic patterns are not changed but the activities of enzymes relating endogeneous respiration and autofermentation is activated. It is to be considerable to distiguish endogeneous respiration and autofermentation from exogeneous respiration and fermentation on irradiation, for membrane permeability changes and loses out carbohydrate by ionizing radiation.

• Journal of the Korean Magnetic Resonance Society
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• v.21 no.1
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• pp.31-43
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• 2017

Together with radiotherapy, chemotherapy using cytotoxic agents is one of the most common therapies in cancer. Metabolic changes in cancer cells are drawing much attention recently, but the metabolic alterations by anticancer agents have not been much studied. Here, we investigated the effects of commonly used cytotoxic agents on lung normal cell MRC5 and lung cancer cell A549. We employed cis-plastin, doxorubicin, and 5-Fluorouracil and compared their effects on the viability and metabolism of the normal and cancer cell lines. We first established the concentration of the cytotoxic reagents that give differences in the viabilities of normal and cancer cell lines. In those conditions, the viability of A549 decreased significantly, whereas that of MRC5 remained unchanged. To study the metabolic alterations implicated in the viability differences, we obtained the metabolic profiles using $^1H$-NMR spectrometry. The $^1H$-NMR data showed that the metabolic changes of A549 cells are more remarkable than that of MRC5 cells and the effect of 5-FU on the A549 cells is the most distinct compared to other treatments. Heat map analysis showed that metabolic alterations under treatment of cytotoxic agents are totally different between normal and cancer cells. Multivariate analysis and weighted correlation network analysis (WGCNA) revealed a distinctive metabolite signature and hub metabolites. Two different analysis tools revealed that the changes of cell metabolism in response to cytotoxic agents were highly correlated with the Warburg effect and Reductive lipogenesis, two pathways having important effects on the cell survival. Taken together, our study addressed the correlation between the viability and metabolic profiles of MRC5 and A549 cells upon the treatment of cytotoxic anticancer agents.

• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.198-204
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• 2004

Tumor cell proliferation is considered to be a useful prognostic indicator of tumor aggressiveness and tumor response to therapy but in vitro measurement of individual proliferation is complex and tedious work. PET imaging provides a noninvasive approach to measure tumor growth rate in situ. Early approaches have used $^{18}F$-FDG or methionine to monitor proliferation status. These 2 tracers detect changes in glucose and amino acid metabolism, respectively, and therefore provide only an indirect measure of proliferation status. More recent studies have focused on DNA synthesis itself as a marker of cell proliferation. Cell lines and tissues with a high proliferation rate require high rates of DNA synthesis. $[^{11}C]Thymidine$ was the first radiotracer for noninvasive imaging of tumor proliferation. The short half-life of $^{11}C$ and rapid metabolism of $[^{11}C]Thymidine$ in vivo make the radiotracer less suitable for routing use. Halogenated thymidine analogs such as 5-iodo-2-deoxyuridine (IUdR) can be successfully used as cell proliferation markers for in vitro studies because these compounds are rapidly incorporated into newly synthesized DNA. IUdR has been evaluated as a potential in vivo tracer in nuclear medicing but the image qualify and the calculation of proliferation rates are impaired by its rapid in vivo degradation. Hence, the thymidine analog $3'-deoxy-3'-^{18}F-fluorothymidine$ (FLT) was recently introduced as a stable proliferation marker with a suitable nuclide half-life and stable in vivo. $[^{18}F]FLT$ is phosphorylated to 3-fluorothymidine monophosphate by thymidine kinase 1 and reflects thymidine kinase 1 activity in proliferating cell. $[^{18}F]FLT$ PET is feasible in clincal use and well correlates with cellular proliferation. Choline is a precursor for the biosynthesis of phospholipids (in particular, phosphatidylcholine), which is the essential component of all eukaryotic cell membranes and $[^{11}C]choline$, which is a new marker for cellular proliferation.

• Journal of Ginseng Research
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• v.34 no.3
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• pp.192-197
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• 2010

Recent studies have indicated that $\beta$-cell dysfunction and insulin resistance are important factors in the development of type 2 diabetes. The present study investigated the effect of extracts from different parts of white, Taegeuk, and red ginseng root on insulin-stimulated glucose uptake in muscle cells and proliferation of $\beta$-cells. Extracts of the fine roots of Taegeuk ginseng significantly enhanced glucose uptake compared with the control. White ginseng lateral root extracts enhanced insulin-induced glucose uptake. Proliferation of $\beta$-cells was significantly increased by Taegeuk ginseng main and lateral root extracts and by red ginseng lateral and fine root extracts. In conclusion, different root parts of white, Taegeuk, and red ginseng differentially affect glucose uptake and pancreatic $\beta$-cell proliferation.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.890-897
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• 2006

In inflammatory responses, induction of cytokines and other immune regulator genes in macrophages by pathogen-associated signal such as lipopolysaccharide (LPS) plays a crucial role. In this study, the gene expression profile changes by LPS treatment in the macrophage/monocyte lineage cell line RAW264.7 was investigated. A 60-mer oligonucleotide microarray of which probes target 32381 mouse genes was used. A reverse transcription-in vitro translation labeling protocol and a chemileuminescence detection system were employed. The mRNA expression levels in RAW264.7 cells treated for 6 h with LPS and the control vehicle were compared. 747 genes were up-regulated and 523 genes were down-regulated by more than 2 folds. 320 genes showing more than 4-fold change by LPS treatment were further classified for the biological process, molecular function, and signaling pathway. The biological process categories that showed high number of increased genes include the immunity and defense, the nucleic acid metabolism, the protein metabolism and modification, and the signal transduction process. The chemokine-cytokine signaling, interleukin signaling, Toll receptor signaling, and apoptosis signaling pathways involved high number of genes differentially expressed in response to LPS. These expression profile data provide more comprehensive information on LPS-target genes in RAW264.7 cells, which will be useful in comparing gene expression changes induced by extracts and compounds from anti-inflammatory medicinal herbs.