• Development and Reproduction
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• v.13 no.1
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• pp.13-23
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• 2009

Recent advances in cell biological and genetic researches have revealed that mitochondrial morphology is highly dynamic and regulated by multiple molecular factors including dynamin-related proteins (DRPs). Considering that the mitochondria play critical roles in the cellular metabolism via ATP synthesis, calcium homeostasis in cooperation with endoplasmic reticulum, and apoptosis, the failure of mitochondrial dynamics is infrequently related to the failure in the normal growth and cellular integrity. In this respect, alteration of mitochondrial dynamics may greatly affect the development of nervous system. In this short review, we discussed molecules involved in the control of mitochondrial dynamics, and provide some perspectives on their significance in the neuronal development.

• Molecules and Cells
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• v.44 no.5
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• pp.335-341
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• 2021

Zinc is an essential micronutrient with crucial roles in multiple facets of biological processes. Dysregulated zinc homeostasis impairs overall immune function and resultantly increases susceptibility to infection. Clinically, zinc supplementation is practiced for treatment of several infectious diseases, such as diarrhea and malaria. Recent focus on zinc as a beneficial element for immune system support has resulted in investigation of the immunomodulatory roles of zinc in a variety of immune cells. Besides its classical role as a cofactor that regulates the structural function of thousands of proteins, accumulating evidence suggests that zinc also acts, in a manner similar to calcium, as an ionic regulator of immune responses via participation as an intracellular messenger in signaling pathways. In this review, we focus on the role of zinc as a signaling molecule in major pathways such as those downstream of Toll-like receptors-, T cell receptor-, and cytokine-mediated signal transduction that regulate the activity and function of monocytes/macrophages and T cells, principal players in the innate and adaptive immune systems.

• Journal of Microbiology and Biotechnology
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• v.30 no.12
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• pp.1835-1842
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• 2020

Ergosterol, an essential constituent of membrane lipids of yeast, is distributed in both the cell membrane and intracellular endomembrane components such as vacuoles. Honokiol, a major polyphenol isolated from Magnolia officinalis, has been shown to inhibit the growth of Candida albicans. Here, we assessed the effect of honokiol on ergosterol biosynthesis and vacuole function in C. albicans. Honokiol could decrease the ergosterol content and upregulate the expression of genes related with the ergosterol biosynthesis pathway. The exogenous supply of ergosterol attenuated the toxicity of honokiol against C. albicans. Honokiol treatment could induce cytosolic acidification by blocking the activity of the plasma membrane Pma1p H+-ATPase. Furthermore, honokiol caused abnormalities in vacuole morphology and function. Concomitant ergosterol feeding to some extent restored the vacuolar morphology and the function of acidification in cells treated by honokiol. Honokiol also disrupted the intracellular calcium homeostasis. Amiodarone attenuated the antifungal effects of honokiol against C. albicans, probably due to the activation of the calcineurin signaling pathway which is involved in honokiol tolerance. In conclusion, this study demonstrated that honokiol could inhibit ergosterol biosynthesis and decrease Pma 1p H+-ATPase activity, which resulted in the abnormal pH in vacuole and cytosol.

• International Journal of Oral Biology
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• v.46 no.1
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• pp.39-44
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• 2021

This study aimed to investigate whether neurotransmitter receptors in the nervous system were also expressed in oral keratinocytes. Expressions of various neurotransmitter receptor genes in immortalized mouse oral keratinocyte (IMOK) cells were examined by reverse transcriptase polymerase chain reaction. IMOK cells expressed calcitonin gene-related peptide (CGRP) receptor subunit genes Ramp1 and Ramp3 and glutamate receptor subunit genes Grina, Gria3, Grin1, Grin2a, and Grin2d. Moreover, IMOK cells expressed Adrb2 and Chrna5 that encode beta 2 adrenergic receptor and cholinergic receptor nicotinic alpha 5 for sympathetic and parasympathetic neurotransmitters, respectively. The expression of Bdkrb1 and Ptger4, which encode receptors for bradykinin and prostaglandin E2 involved in inflammatory responses, was also observed at low levels. Expressions of Ramp1 and Grina in the mouse gingival epithelium were also confirmed by immunohistochemistry. When the function of neurotransmitter receptors expressed on IMOK cells was tested by intracellular calcium response, CGRP, glutamate, and cholinergic receptors did not respond to their agonists, but the bradykinin receptor responded to bradykinin. Collectively, oral keratinocytes express several neurotransmitter receptors, suggesting the potential regulation of oral epithelial homeostasis by the nervous system.

• Clinical and Experimental Reproductive Medicine
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• v.50 no.1
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• pp.1-11
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• 2023

In reproduction, mitochondria produce bioenergy, help to synthesize biomolecules, and support the ovaries, oogenesis, and preimplantation embryos, thereby facilitating healthy live births. However, the regulatory mechanism of mitochondria in oocytes and embryos during oogenesis and embryo development has not been clearly elucidated. The functional activity of mitochondria is crucial for determining the quality of oocytes and embryos; therefore, the underlying mechanism must be better understood. In this review, we summarize the specific role of mitochondria in reproduction in oocytes and embryos. We also briefly discuss the recovery of mitochondrial function in gametes and zygotes. First, we introduce the general characteristics of mitochondria in cells, including their roles in adenosine triphosphate and reactive oxygen species production, calcium homeostasis, and programmed cell death. Second, we present the unique characteristics of mitochondria in female reproduction, covering the bottleneck theory, mitochondrial shape, and mitochondrial metabolic pathways during oogenesis and preimplantation embryo development. Mitochondrial dysfunction is associated with ovarian aging, a diminished ovarian reserve, a poor ovarian response, and several reproduction problems in gametes and zygotes, such as aneuploidy and genetic disorders. Finally, we briefly describe which factors are involved in mitochondrial dysfunction and how mitochondrial function can be recovered in reproduction. We hope to provide a new viewpoint regarding factors that can overcome mitochondrial dysfunction in the field of reproductive medicine.

• Journal of Ginseng Research
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• v.42 no.2
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• pp.165-174
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• 2018

Background: Extended endoplasmic reticulum (ER) stress may initiate apoptotic pathways in cancer cells, and ER stress has been reported to possibly increase tumor death in cancer therapy. We previously reported that caspase-8 played an important role in compound K-induced apoptosis via activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation in HL-60 human leukemia cells. The mechanisms leading to apoptosis in A549 and SK-MES-1 human lung cancer cells and the role of ER stress have not yet been understood. Methods: The apoptotic effects of compound K were analyzed using flow cytometry, and the changes in protein levels were determined using Western blot analysis. The intracellular calcium levels were monitored by staining with Fura-2/AM and Fluo-3/AM. Results: Compound K-induced ER stress was confirmed through increased phosphorylation of $eIF2{\alpha}$ and protein levels of GRP78/BiP, XBP-1S, and $IRE1{\alpha}$ in human lung cancer cells. Moreover, compound-K led to the accumulation of intracellular calcium and an increase in m-calpain activities that were both significantly inhibited by pretreatment either with BAPTA-AM (an intracellular $Ca^{2+}$ chelator) or dantrolene (an RyR channel antagonist). These results were correlated with the outcome that compound K induced ER stress-related apoptosis through caspase-12, as z-ATAD-fmk (a specific inhibitor of caspase-12) partially ameliorated this effect. Interestingly, 4-PBA (ER stress inhibitor) dramatically improved the compound K-induced apoptosis. Conclusion: Cell survival and intracellular $Ca^{2+}$ homeostasis during ER stress in human lung cancer cells are important factors in the induction of the compound K-induced apoptotic pathway.

• Korean Journal of Veterinary Research
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• v.36 no.3
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• pp.709-718
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• 1996

This experiment was carried out to clarify the effect of lead poisoning on the lead and essential trace elements homeostasis of tissues in rats. Fifty female Wistar rats, 7 weeks old, were divided into four experimental groups(B, C, D, and E) and a control(A). The four experimental groups received diets contaminated artificially with 10 (B group), 100 (C group), 1,000 (D group) and 5,000 (E group) ${\mu}g/g$ of lead as lead acetate, respectively. The control group received normal diet. Rats were necropsied on the 4th or 8th week of experimental periods and heart, liver, spleen, kidney, muscle, lung and hair were taken. The tissues were analysed for lead, copper, zinc, iron and calcium content by atomic absorption spectrophotometry. From these experiments following results ware obtained ; In C group, lead content of the heart, liver, kidney and hair were significantly increased both on the 4th and 8th week of experiment. In D and E group, lead content of all tissues including heart, liver, spleen, kidney, muscle, hair and lung were significantly increased in accordance with the lead contamination both on the 4th and 8th week of experiment. In C group, copper content of tissues were significantly increased in the heart, liver, kidney and lung on the 4th week and all tissues on the 8th week of experimental periods. In D and E group, copper content of the liver were significantly increased both on the 4th and 8th week of experiment. But the copper content of tissues were gradually decreased compared with C group in accordance with the lead contamination. Especially the content in spleen, heart or kidney were significantly decreased compared with the control group. The zinc content of kidney, heart, or spleen were decreased in D and E groups whereas the iron and calcium content showed no significant change.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.6
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• pp.539-546
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• 1999

Bone is a complex tissue in which resorption and formation continue throughout life. The bone tissue contains various types of cells, of which the bone forming osteoblasts and bone resorbing osteoclasts are mainly responsible for bone remodeling. Periodontal disease represents example of abnormal bone remodeling. Osteoclasts are multinucleated cells present only in bone. It is believed that osteoclast progenitors are hematopoietic origin, and they are recruited from hematopoietic tissues such as bone marrow and circulating blood to bone. Cells present in the osteoclast microenvironment include marrow stromal cells, osteoblasts, macrophages, T-lymphocytes, and marrow cells. These cells produce cytokines that can affect osteoclast formation. In vitro model systems using bone marrow cultures have demonstrated that $IL-l{\beta},\;IL-3,\;TNF-{\alpha},$ bFGF can stimulate the formation of osteoclasts. In contrast, IL-4 inhibits osteoclast formation. Knowledge of cytokines and bFGF that affect osteoclast formation and their capacity to modulate the bone-resorbing process should provide critical insights into normal calcium homeostasis and disorders of bone turnover such as periodontal disease, osteoporosis and Paget's disease.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.6
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• pp.509-516
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• 2014

Radiation therapy for variety of human solid tumors utilizes mechanism of cell death after DNA damage caused by radiation. In response to DNA damage, cytochrome c was released from mitochondria by activation of pro-apoptotic Bcl-2 family proteins, and then elicits massive $Ca^{2+}$ release from the ER that lead to cell death. It was also suggested that irradiation may cause the deregulation of $Ca^{2+}$ homeostasis and trigger programmed cell death and regulate death specific enzymes. Thus, in this study, we investigated how cellular $Ca^{2+}$ metabolism in RKO cells, in comparison to radiation-resistant A549 cells, was altered by gamma (${\gamma}$)-irradiation. In irradiated RKO cells, $Ca^{2+}$ influx via activation of NCX reverse mode was enhanced and a decline of $[Ca^{2+}]_i$ via forward mode was accelerated. The amount of $Ca^{2+}$ released from the ER in RKO cells by the activation of $IP_3$ receptor was also enhanced by irradiation. An increase in $[Ca^{2+}]_i$ via SOCI was enhanced in irradiated RKO cells, while that in A549 cells was depressed. These results suggest that ${\gamma}$-irradiation elicits enhancement of cellular $Ca^{2+}$ metabolism in radiation-sensitive RKO cells yielding programmed cell death.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.4
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• pp.531-536
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• 2002

We investigated the exercise-induced changes in the serum concentration of several minerals in horses. Four welltrained Thoroughbred horses performed exercise for 5 d. The blood hemoglobin (Hb) concentration increased during exercise, recovered to the pre-exercise level immediately after cooling down and did not change again up till the end of experiment. The changes in serum zinc (Zn) and copper (Cu) concentrations were similar to those of blood Hb during the experiment. The serum magnesium (Mg), inorganic phosphorus (Pi) and iron (Fe) concentrations also increased during exercise. Though the serum Pi concentration recovered to the pre-exercise level immediately after the cooling down, it decreased further before the end of the experiment. The serum Mg concentration was lower immediately after cooling down than its pre-exercise level but gradually recovered from the temporal reduction. The recovery of the serum Fe concentration was delayed compared to that of other minerals and recovered 2 h after cooling down. The serum calcium (Ca) concentration did not change during exercise but rapidly decreased after cooling down. As a result, it was lower immediately after cooling down than its pre-exercise level. It recovered, however, to the pre-exercise level 2 h after cooling down. The temporal increase in the serum concentrations of all minerals except Ca is considered to result from hemoconcentration induced by exercise and the stable concentration of the serum Ca during exercise is possibly due to its strict regulation of homeostasis. These results indicate that the serum concentration of each mineral responds differently to exercise in horses, which may be due to the difference in metabolism among these minerals.