• Title/Summary/Keyword: Cell senescence

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Anticancer Drugs at Low Concentrations Upregulate the Activity of Natural Killer Cell

  • Hyeokjin Kwon;Myeongguk Jeong;Yeeun Kim;Go-Eun Choi
    • Biomedical Science Letters
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    • v.29 no.3
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    • pp.178-183
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    • 2023
  • Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. Regulation of the cytotoxic activity of NK cells relies on integrated interactions between inhibitory receptors and numerous activating receptors that act in tandem to eliminate tumor cells efficiently. Conventional chemotherapy is designed to produce an anti-proliferative or cytotoxic effect on early tumor cell division. Therapies designed to kill cancer cells and simultaneously maintain host anti-tumor immunity are attractive strategies for controlling tumor growth. Depending on the drug and dose used, several chemotherapeutic agents cause DNA damage and cancer cell death through apoptosis, immunogenic cell death, or other forms of non-killing (i.e., mitotic catastrophe, senescence, autophagy). Among stress-induced immunostimulatory proteins, changes in the expression levels of NK cell activating and inhibitory ligands and tumor cell death receptors play an important role in the detection and elimination by innate immune effectors including NK cells. Therefore, we will address how these cytotoxic lymphocytes sense and respond to high and low concentrations of drug-induced stress to the drug cisplatin, among the various types of drugs that contribute to their anticancer activity.

Recent Trends on Telomerase Activators, Sirtuin Activators, and Senolytics as a Potential Anti-aging Agent (잠재적인 항노화제로 텔로머레이즈 활성화제, 서르튜언 활성화제, 세노릭틱스에 대한 최신 동향)

  • Kim, Moon-Moo
    • Journal of Life Science
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    • v.30 no.9
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    • pp.819-825
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    • 2020
  • All living organisms exhibit the characteristics of aging, such as skin wrinkle formation, muscle degeneration, cataracts, and hair graying as the number of aged cells increases over time. Senescence, which is known as a key cause of aging, is directly related to the aging of living organisms because cells are aged by external and internal factors and eventually cell proliferation is stopped. Senescence is caused by the gradual shortening of the telomere with cell division, and lifespan is determined by the length of the telomere. Recently, it has been found that the histone deacetylase, which can influence gene expression, is not only involved in yeast but also deeply involved in anti-aging mechanisms in both C. elegans and humans. It was also discovered that old cells play a decisive role in the aging phenomenon, and it has been reported that it is possible to promote the proliferation of young cells and delay aging by removing these senescent cells from the inside. Therefore, in order to develop potential anti-aging agents in the future, research should begin with an in-depth study of telomerase activators, sirtuin activators, and senolytics.

IL-15 in T-Cell Responses and Immunopathogenesis

  • Hoyoung Lee;Su-Hyung Park;Eui-Cheol Shin
    • IMMUNE NETWORK
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    • v.24 no.1
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    • pp.11.1-11.18
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    • 2024
  • IL-15 belongs to the common gamma chain cytokine family and has pleiotropic immunological functions. IL-15 is a homeostatic cytokine essential for the development and maintenance of NK cells and memory CD8+ T cells. In addition, IL-15 plays a critical role in the activation, effector functions, tissue residency, and senescence of CD8+ T cells. IL-15 also activates virtual memory T cells, mucosal-associated invariant T cells and γδ T cells. Recently, IL-15 has been highlighted as a major trigger of TCR-independent activation of T cells. This mechanism is involved in T cell-mediated immunopathogenesis in diverse diseases, including viral infections and chronic inflammatory diseases. Deeper understanding of IL-15-mediated T-cell responses and their underlying mechanisms could optimize therapeutic strategies to ameliorate host injury by T cell-mediated immunopathogenesis. This review highlights recent advancements in comprehending the role of IL-15 in relation to T cell responses and immunopathogenesis under various host conditions.

Vitamin C Promoted Liver Regeneration Following Partial Hepatectomy-induced Hepatic Injury in Senescence Marker Protein-30-deficient Mice (비타민 C 투여는 간 부분절제술에 의한 간 재생을 촉진 시킴)

  • Han, Seon Young;Hwang, Meeyul;Kim, Ah-Young;Lee, Eun-Mi;Lee, Eun-Joo;Lee, Myeong-Mi;Sung, Soo-Eun;Kim, Sang-Hyeob;Jeong, Kyu-Shik
    • Journal of Life Science
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    • v.25 no.3
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    • pp.336-344
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    • 2015
  • The capacity for liver regeneration involves a variety of nutritional factors. Vitamin C has multiple metabolic and antioxidant functions. In this study, we investigated the role of vitamin C in liver regeneration following hepatectomy in senescence marker protein (SMP)-30 knockout (KO) mice. Partial hepatectomy was performed by resecting the median and left lateral lobes of mice. Vitamin C accelerated liver recovery in SMP30 KO mice treated with vitamin C (KV). The livers of the KV mice exhibited lower levels of aspartate aminotransferase and lower injury than those of the KO mice. Increased type II transforming growth factor-β receptor (TGF-βRII)-mediated regeneration signaling was accompanied by HGF and cMet in the KV but not the KO mice. Consistent with this, the expression of cell cycle regulatory proteins, including cyclin D1 and proliferating cell nuclear antigen (PCNA), increased rapidly in the KV mice. Enhanced activation of ERK and GSK-3β proteins and a significantly increased number of binuclear hepatocytes were also detected in the livers of the KV mice. Moreover, the KV mice synthesized the highest levels of albumin. These data suggest that treating SMP30 knockout mice with vitamin C resulted in earlier recovery and liver regeneration by activation of the regeneration system.

Comparative Analysis on Antioxidant Activity in Various Human Skin Fibroblasts and Mesenchymal Stem Cells (사람의 피부 섬유아세포 및 중간엽 줄기세포에서 항산화 활성의 반응에 대한 비교 분석)

  • Kong, Ji-Weon;Park, Ryeok;Park, Joon-Woo;Lee, Joo-Yeong;Choi, Yeon-Joo;Moon, Sun-Ha;Kim, Hyeon-Ji;Jeon, Byeong-Gyun
    • Journal of the Korean Applied Science and Technology
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    • v.36 no.2
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    • pp.394-406
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    • 2019
  • The cellular senescence may be due to damage by the reactive oxygen species (ROS). This study has compared the antioxidant activity in the human cell lines of various origins, including 10S and 50S-derived normal skin fibroblasts, and 10S bone marrow, dental tissue and adipose-derived adult stem cells. After being exposed to $H_2O_2$, half inhibitory concentration ($IC_{50}$) values by cytotoxicity assay was significantly (P<0.05) lower in 50S-derived skin fibroblasts, than in 10S-derived skin fibroblasts and various adult stem cell lines. The cell population doubling time (PDT) and the cell frequency with high senescence associated-${\beta}$-galactose activity were remarkably increased in 50S-derived fibroblasts exposed to 50 ppm $H_2O_2$ for 7 days, than those of 10S-derived fibroblasts and various adult stem cell lines. Further, the expression level of antioxidant-related genes, glutathione peroxidase (GPX) and catalase (CAT), was investigated in 10S and 50S-derived skin fibroblasts, and 10S-derived various adult stem cells by reverse transcription polymerase chain reaction (RT-PCR). The expression level of GPX was higher in most of cell lines, compared to CAT, and a significantly (P<0.05) higher expression level of GPX was observed in 10S-derived skin fibroblasts and adult stem cell lines, compared to 50S-derived skin fibroblasts. We concluded that old-aged skin fibroblasts seemed to be less resistant against ROS than young-aged skin fibroblasts and adult stem cells.

Changes of RNA synthesis in Anther Wall of Brassica napus during Male Gametogenesis

  • Kim, Moon-Za
    • Journal of Plant Biology
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    • v.38 no.1
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    • pp.25-32
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    • 1995
  • The distribution of RNA in the anther wall of Brassica napus during male gametogenesis was followed by 3H-uridine autoradiography. Silver grain(SG) density was not above background in the anther wall just after microspore was released from tetrad callose wall. Significant accumulation of SGs occurred in tapetum, endothecium, and epidermis before microspore vacuolation. Accumulation of RNA in the tapetal cells was peak before the vaculation occurred in the microspore. With the onset of tapetal senescence at the partially vacuolated microspore stage, SGs decreased and they completely disappeared in the tapetum at the bicelled pollen stage. Accumulation of RNA in the endothecial cells was peak after the microspore mitosis and continued just after the generative cell mitosis. Appreciable SGs also occurred in cells of epidermis from nonvacuolate microspore stage to bicelled pollen stage. During this period, SG density was almost same and was not high as compared with tapetum or endothecium. At tricelled mature pollen stage, no incorporation occurred in anther wall. SGs were found mostly over the nucleouls and chromation of the cell nuclei.

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Mild Hyperthermia-induced Cell Cycle Arrest under P53-dependent Pathway in Human Cells

  • Jung, Hwa-Jin;Yim, Sung-Vin;Park, Seungjoon;Jung, Joo-Ho;Jung, Jee-Chang;Seo, Young-Rok
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.114-114
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    • 2003
  • p53 has identified as a tumor suppressor protein to protect cells from DNA damage. p53, also well known for a transcription factor, can activate genes such as p21, bax, gadd45 and induce a number of the responses such as differentiation, senescence, DNA repair, apoptosis and the inhibition of angiogenesis to protect cells. Many mechanisms of p53 activation have been studied.(omitted)

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Protective Effects of Bifidobacterium bifidum Culture Supernatants and Intracellular Cell-Free Extracts on Human Dermal Fibroblasts against UV-B Irradiation (인간 진피섬유아세포에서 Bifidobacterium bifidum 배양액 및 추출액의 자외선B에 대한 보호 효능)

  • Gwon, Gi Yeong;Park, Gwi Gun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.7
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    • pp.801-808
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    • 2017
  • The present study investigated the protective effects of Bifidobacterium bifidum culture supernatants (BbSC) and intracellular cell-free extracts (BbICFE) on human dermal fibroblasts (HDFs) against ultraviolet-B (UV-B) irradiation. HDFs were treated with UV-B, UV-B+BbCS, and UV-B+BbICFE. Treatment of UV-B-irradiated HDFs with BbCS and BbICFE significantly increased cell viability compared to UV-B-irradiated HDFs. BbCS treatment reduced senescence in HDFs by approximately 40.0%. Moreover, sub-G1 phase was significantly reduced in BbCS- and BbICFE-treated HDFs (3.3% and 4.5%, respectively). The effect of UV-B on oxidative damage of HDFs was measured by dichlorofluorescin diacetate. Fluorescence intensity significantly increased in UV-B-irradiated HDFs. Inhibition of cellular reactive oxygen species in HDFs treated with 0.01% BbCS was the highest at 34.1%. Levels of p21 and p53 protein expression induced by UV-B irradiation were reduced by treatment with BbCS and BbICFE (47.0% and 35.6%, respectively). These results show that BbCS and BbICFE reduce UV-B-induced cellular senescence and apoptosis in HDFs. Thus, BbCS and BbICFE can be used as potential agents for protection of UV-B-induced skin cell damage.

Development of Cosmetic Ingredient by Fermented Paprika Juice (파프리카 발효즙의 화장품 소재개발 연구)

  • Bae, Soo Jung;Song, Min Hyeon;Oh, Jung Young;Bae, Jun Tae;Kim, Jin Hwa;Lee, Geun Soo
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.44 no.2
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    • pp.117-124
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    • 2018
  • In this study, cosmetic materials were developed using a new method of making juice through the fermentation of raw natural materials with microorganisms in order to supplement the advantages and disadvantages of an organic solvent extraction method and a microbial fermentation method. The natural products were selected from two colors (red, green) of paprika known to be rich in various colors and vitamins. The microorganisms used for fermentation were fermented by inoculating paprika with lactic acid bacteria (Lactobacillus plantarum) having sugar-hydrolyzed ability. First, we investigated the changes of physiologically active substances of two kinds of paprika juice and two kinds of fermented paprika juice. Total phenols content and total flavonoids content were higher in the fermented paprika juice than in the paprika juice, and especially in the fermented red paprika juice. Free radical scavenging effect and lipid peroxidation inhibitory effect were also showed an excellent antioxidative effect on paprika fermented juice, among which the effect of red paprika fermentation juice was the highest. The expression of MMP-1 in fermented red paprika juice with high antioxidant activity was inhibited by concentration-dependent expression of MMP-1 mRNA and MMP-1 protein. In the glycation experiments with aging, the anti-glycation effect of fermented paprika juice was highly inhibited by the production of advanced glycation end-products (AGEs), which was closely related to the antioxidant effect. In addition, the activity of senescence-associated ${\beta}$-galactosidase (SA-${\beta}$-gal), an indicator of cell senescence, was measured using human dermal fibroblast (HDF). The results showed that the cell senescence was inhibited when the cells were treated with fermented paprika juice. In conclusion, fermented paprika juice using lactic acid bacteria showed better antioxidative and anti-aging effects than paprika juice. Among them, fermented red paprika juice has the best antioxidant and anti-aging effect and can be applied as natural new material of antioxidant and anti-aging.

Telomerase: Key to Mortal or Immortal Road

  • Yang, Eun-Young;Sung, Young Hoon;Lee, Han-Woong
    • IMMUNE NETWORK
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    • v.2 no.4
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    • pp.183-188
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    • 2002
  • Gradual attrition of telomere to a critical short length elicits successive cellular response of cellular senescence and crisis. Cancer cells evade this process by maintaining functional telomeres via one of two known mechanisms of telomere maintenance. The first and most frequent mechanism involves reactivation of enzyme activity of telomerase, a ribonucleoprotein complex mainly via transcriptional up-regulation of TERT, a catalytic subunit of telomerase complex. The second mechanism utilizes telomerase-independent way termed ALT (for Alternative Lengthening of Telomere), which possibly involves recombination pathways. Thus master key for cellular immortalization is supposed to possess adequate telomere reserves. Indeed, telomerase can alone induce the immortalization under culture on feeder cell layers without generally known inactivation mechanism of tumor suppressor genes. Including this phenomena, this review will focus on telomerase and telomere-associated proteins, thereby implication of these proteins for cellular immortalization processes.