• The Korean Journal of Physiology and Pharmacology
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• 제25권4호
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• pp.297-305
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• 2021

Luteolin, a sort of flavonoid, has been reported to be involved in neuroprotective function via suppression of neuroinflammation. In this study, we investigated the protective effect of luteolin against oxidative stress-induced cellular senescence and its molecular mechanism using hydrogen peroxide (H₂O₂)-induced cellular senescence model in House Ear Institute-Organ of Corti 1 cells (HEI-OC1). Our results showed that luteolin attenuated senescent phenotypes including alterations of morphology, cell proliferation, senescence-associated 𝛽-galactosidase expression, DNA damage, as well as related molecules expression such as p53 and p21 in the oxidant challenged model. Interestingly, we found that luteolin induces expression of sirtuin 1 in dose- and time-dependent manners and it has protective role against H₂O₂-induced cellular senescence by upregulation of sirtuin 1 (SIRT1). In contrast, the inhibitory effect of luteolin on cellular senescence under oxidative stress was abolished by silencing of SIRT1. This study indicates that luteolin effectively protects against oxidative stress-induced cellular senescence through p53 and SIRT1. These results suggest that luteolin possesses therapeutic potentials against age-related hearing loss that are induced by oxidative stress.

• 한국동물학회지
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• 제37권2호
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• pp.232-239
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• 1994

RecA protein plans a central role in homologous recombination and DNA repair in Escherichia cofi (E. colD. The function 8nd structure of this protein are universal in prokarvotes and also conserved in eukaryotes such as yeast. The RecA-like protein with 74 lInDa in size has already been identified and purified from a fission yeast Schizosaccharomyces pombe (5. pommel (Lee, 19911. From this study it was revealed that the RecA-like protein of 5. pombe was highly inducible to various DNA damaging agents and inhibitors of nucleotide pool svnthesizins enzymes. The cellular level of the 5. pombe RecA-like protein wi,u markedly increased, upto 5- to 10-fold, by treatment with various DNA-damains agents including ultraviolet (UV) light, methyl methanesulfonate WS),4-nitroquinoline-1-oxide (4-NQO), and mitomycin-C (MMC), similar to E. cofi RecA protein. Interestingly, the protein level was also increased by inhibitors of nucleotide pool forming enzlwnes such as methotrexate (MTX) and hvdroxvurea (HU). The most effective doses for the inducibility of 4-NQO, MMS, W, MMC, MTX, and HU were 0.2 Ug/ml, 30 mM, 200 J/ma, 0.4 $\mus/ml,$ 1 Ug/ml, and 100 mM, respectively. The range of effective duration time for the inducibilitv of RecA-like protein was from 270 to 450 mins. These results suggest that the 5. pombe RecA-like protein also platys an imortant role in cellular responses to DNA damage as in E. coli system.

• 한국수의병리학회지
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• 제2권1호
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• pp.37-46
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• 1998

It has been known that $\gamma$-irradiation usually induces cell death in regenerating stem cell in normal tissues like skin, intestine and hematopoietic organ. The experiment were carried out to evaluate the early response of radiation injury in radiosensitive and intermediate radiosensitive tissues in feeding and starving rats with the doses of 3.5 and 7.0 Gy. The results of the study showed that the histological phenomenon was apoptosis in the doses of the radiation as the early response of tissue injury. Apoptosis were showed organ-specific and cellular specific responses suggesting that the selection of apoptosis be exactly focused on highly renewal organs and cells. It was interesting that the rats starved for 72 hours prior to irradiation induced less apoptosis in liver than fed rats. As for cellular responses it appeared that apoptotic cells were mostly distributed in ductal or periportal cells in liver of feeding rats unlikely in liver of Starving rots which showed no difference in zonal distribution. In salivary gland apoptotic cells in fed rats were highly induced in intercalating and ductal cell population than in acinar cell population although unlikely in starved rats. This study showed the value of apoptosis using the detection system of TUNEL for evaluating cellular damage after radiation injury and the diminished effect of starvation on cell damage after ionizing irradiation.

• Journal of Nutrition and Health
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• 제37권9호
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• pp.794-800
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• 2004

Deer Antler has been known for its traditional oriental medicinal properties and has been widely used to promote growth, boost immune function, treat blood loss and chronic joint pain. Recent study showed imported (New Zealand) Deer Antler was beneficial in reducing the side effects of cancer treatments. However, there was no intervention study conducted on the effect of Korean Deer Antler on reducing the oxidative stress to patients with diabetes. One of the sensitive ways to measure endogenous oxidative stress is by measuring cellular DNA damage using single cell gel electrophoresis (COMET assay). This study was conducted to investigate the possible beneficial effect of commercial Deer Antler drink (provided by Chung-yang Deer Farm) on lymphocyte DNA damage and blood glucose of diabetic patients. Ten patients (4 men, 6 women) participated in the study and consumed 2 pouches of Deer Antler drink every day for 20 days. Blood was collected on the morning before and after the intervention for lymphocyte isolation and blood glucose analysis. Both systolic and diastolic blood pressure showed a tendency to decrease but did not reach statistical significance after the trial. Blood glucose level was not affected by the supplementation. After the intervention, over 50% reduction were noted in the cellular DNA damage, expressed as tail length (TL) and tail moment (TM: tail length ${\times}$ percent tail DNA) . Although we did not obtain beneficial effect on lowering blood glucose levels in the patients, this results suggest that Deer Antler may initially act in protecting endogenous DNA damage in short-term experiment.

• BMB Reports
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• 제47권4호
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• pp.209-214
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• 2014

Ultraviolet B (UVB) radiation induces the production of reactive oxygen species (ROS) that promote apoptotic cell death. We showed that cytosolic $NADP^+$-dependent isocitrate dehydrogenase (IDPc) plays an essential role in the control of cellular redox balance and defense against oxidative damage, by supplying NADPH for antioxidant systems. In this study, we demonstrated that knockdown of IDPc expression by RNA interference enhances UVB-induced apoptosis of immortalized human HaCaT keratinocytes. This effect manifested as DNA fragmentation, changes in cellular redox status, mitochondrial dysfunction, and modulation of apoptotic marker expression. Based on our findings, we suggest that attenuation of IDPc expression may protect skin from UVB-mediated damage, by inducing the apoptosis of UV-damaged cells.

• Journal of Microbiology and Biotechnology
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• 제31권2호
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• pp.171-180
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• 2021

Caffeine, a methylxanthine analog of purine bases, is a compound that is largely consumed in beverages and medications for psychoactive and diuretic effects and plays many beneficial roles in neuronal stimulation and enhancement of anti-tumor immune responses by blocking adenosine receptors in higher organisms. In single-cell eukaryotes, however, caffeine somehow impairs cellular fitness by compromising cell wall integrity, inhibiting target of rapamycin (TOR) signaling and growth, and overriding cell cycle arrest caused by DNA damage. Among its multiple inhibitory targets, caffeine specifically interacts with phosphatidylinositol 3-kinase (PI3K)-related kinases causing radiosensitization and cytotoxicity via specialized intermediate molecules. Caffeine potentiates the lethality of cells in conjunction with several other stressors such as oxidants, irradiation, and various toxic compounds through largely unknown mechanisms. In this review, recent findings on caffeine effects and cellular detoxification schemes are highlighted and discussed with an emphasis on the inhibitory interactions between caffeine and its multiple targets in eukaryotic microorganisms such as budding and fission yeasts.

• Toxicological Research
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• 제17권4호
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• pp.249-253
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• 2001

Fumonisin B1, a mycotoxin, is thought to induce esophageal cancer in humans and apoptosis in animal cells by inhibiting ceramide synthase. Dumonisin Bl may also generate reactive oxygen species directly or indirectly, leading to DNA damage and lipid peroxidation. In this study, a DNA fragmentation assay, dichlorofluorescein (DCF) analysis, and single cell gel electrophoresis (SCGE) were used to investigate the involvement of cellular free radicals, specifically hydrogen peroxide, in the DNA damaging activity of fumonisin B1. From an in vitro DNA fragmentation assay, E. coli DNA, damage by fumonisin Bl was increased by the addition of superxide dismutase (SOD) and decreased by catalase. SCGE and DCF analysis in vivo showed that the nuclear DNA damage and intracellular free radicals in cultured rat hepatocytes treated with fumonisin B1 were increased with the concentration of fumonisin Bl . DNA damage and free radical generation were inhibited by the addition of catalase. Fumonisin Bl , in the presence of SOD, produces hydrogen peroxide causing oxidative DNA damage and protein malfunction, leading to genotoxicity and cytotoxicity of the toxin.

• 생물정신의학
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• 제14권4호
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• pp.221-231
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• 2007

Recent researches have shown that important cellular-based autoprotective mechanisms are mediated by heat-shock proteins(HSPs), also called 'molecular chaperones'. HSPs as molecular chaperones are the primary cellular defense mechanism against damage to the proteome, initiating refolding of denatured proteins and regulating degradation after severe protein damage. HSPs also modulate multiple events within apoptotic pathways to help sustain cell survival following damaging stimuli. HSPs are induced by almost every type of stresses including physical and psychological stresses. Our nervous system in the brain are more vulnerable to stress and damage than any other tissues due to HSPs insufficiency. The normal function of HSPs is a key factor for endogenous stress adaptation of neural tissues. HSPs play an important role in the process of neurodevelopment, neurodegeneration, and neuroendocrine regulation. The altered function of HSPs would be associated with the development of several neuropsychiatric disorders. Therefore, an understanding of HSPs activities could help to improve autoprotective mechanism of our neural system. This paper will review the literature related to the significance of HSPs in neuropsychiatric field.

• 한국미생물·생명공학회지
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• 제50권4호
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• pp.441-456
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• 2022

Shiga toxins (Stxs) are major virulence factors from the enterohemorrhagic Escherichia coli (EHEC), a subset of Stx-producing Escherichia coli. Stxs are multi-functional, ribosome-inactivating proteins that underpin the development of hemolytic uremic syndrome (HUS) and central nervous system (CNS) damage. Currently, therapeutic options for the treatment of diseases caused by Stxs are limited and unsatisfactory. Furthermore, the pathophysiological mechanisms underpinning toxin-induced inflammation remain unclear. Numerous works have demonstrated that the various host ribotoxic stress-induced targets including p38 mitogen-activated protein kinase, its downstream substrate Mitogen-activated protein kinase-activated protein kinase 2, and apoptotic signaling via ER-stress sensors are activated in many different susceptible cell types following the regular retrograde transportation of the Stxs, eventually leading to disturbing intercellular communication. Therapeutic options targeting host cellular pathways induced by Stxs may represent a promising strategy for intervention in Stx-mediated acute renal dysfunction, retinal damage, and CNS damage. This review aims at fostering an in-depth understanding of EHEC Stxs-mediated pathogenesis through the toxin-host interactions.

• 대한한의학회지
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• 제20권2호
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• pp.88-97
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• 1999

To characterize the effects of Gilgyung-Tang(GGT) on cellular proliferation and viability of normal lung fibroblast cells, we examined the cell cycle progression and cell cycle-related gene expression in T3891 using a flow cytometry and a quantitative RT-PCR analysis. 1. The significant surpression effect of cellular proliferations of GGT was observed in proportion to a certain concentration and time. 2. GGT was identified to induce apoptotic death of damaged cells by treatment with a DNA-damage agent and etoposide, while it stimulated the recovery of cellular viability of normal cells. 3 The significant reductions of mRNA expression of PCAN, c-Fos treated by GGT were observed. 4. The significant inductions of mRNA expression of p53, CDKN1. Gadd45 treated by GGT were observed. 5. The apoptosis caused by the reduction of Bcl-2 genes was significant and the Bax genes were increased. but the amount of Fas genes were not changed. These results strongly suggest that GGT triggers arrest of the cell cycle at G1 phase, and thus causes an inhibition of cellular proliferation of human normal lung cells through the transcriptional up-regulation of cell cycle inhibitory genes and down-regulation of induction of cell cycle stimulating genes respectably.