• Molecules and Cells
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• 제42권3호
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• pp.252-261
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• 2019

The omega-3 fatty acid docosahexaenoic acid (DHA) is known to induce apoptosis and cell cycle arrest via the induction of reactive oxygen species (ROS) production and endoplasmic reticulum (ER) stress in many types of cancers. However, the roles of DHA in drug-resistant cancer cells have not been elucidated. In this study, we investigated the effects of DHA in cisplatin-resistant gastric cancer SNU-601/cis2 cells. DHA was found to induce ROS-dependent apoptosis in these cells. The inositol 1,4,5-triphosphate receptor ($IP_3R$) blocker 2-aminoethyl diphenylboninate (2-APB) reduced DHA-induced ROS production, consequently reducing apoptosis. We also found that G-protein-coupled receptor 120 (GPR120), a receptor of long-chain fatty acids, is expressed in SNU-601/cis2 cells, and the knockdown of GPR120 using specific shRNAs alleviated DHA-mediated ROS production and apoptosis. GPR120 knockdown reduced the expression of ER stress response genes, similar to the case for the pre-treatment of the cells with N-acetyl-L-cysteine (NAC), an ROS scavenger, or 2-APB. Indeed, the knockdown of C/EBP homologous protein (CHOP), a transcription factor that functions under ER stress conditions, markedly reduced DHA-mediated apoptosis, indicating that CHOP plays an essential role in the anti-cancer activity of DHA. These results suggest that GPR120 mediates DHA-induced apoptosis by regulating $IP_3R$, ROS, and ER stress levels in cisplatin-resistant cancer cells, and that GPR120 is an effective chemotherapeutic target for cisplatin resistance.

• The Journal of Korean Physical Therapy
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• 제20권1호
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• pp.57-65
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• 2008

Purpose: Heat shock proteins (HSPs) are a group of proteins that are activated when cells are exposed to a variety of environmental stresses, such as infection, inflammation, exposure to toxins, starvation, hypoxia, brain injury, or water deprivation. The activation of HSPs by environmental stress plays a key role in signal transduction, including cytoprotection, molecular chaperone, anti-apoptotic effect, and anti-aging effects. However, the precise mechanism for the action of small HSPs, such as HSP27 and mitogen-activated protein kinases (MAPKs: extracellular-regulated protein kinase 1/2 (ERK1/2), p38MAPK, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), is not completely understood, particularly in application of cell stimulators including platelet-derived growth factor (PDGF), angiotensin II (AngII), tumor necrosis factor $\alpha$ (TNF$\alpha$), and $H_2O_2$. This study examined the relationship between stimulators-induced enzymatic activity of HSP27 and MAPKs from rat smooth and skeletal muscles. Methods: 2-dimensional electrophoresis (2DE) and matrix assisted laser desorption ionizationtime-of-flight/time-of-flight (MALDI-TOF/TOF) analysis were used to identify HSP27 from the intact vascular smooth and skeletal muscles. Three isoforms of HSP27 were detected on silver-stained gels of the whole protein extracts from the rat aortic smooth and skeletal muscle strips. Results: The expression of PDGF, AngII, TNF$\alpha$, and $H_2O_2$-induced activation of HSP27, p38MAPK, ERK1/2, and SAPK/JNK was higher in the smooth muscle cells than the control. SB203580 (30${\mu}$M), a p38MAPK inhibitor, increased the level of HSP27 phosphorylation induced by stimulators in smooth muscle cells. Furthermore, the age-related and starvation-induced activation of HSP27 was higher in skeletal muscle cells (L6 myoblast cell lines) and muscle strips than the control. Conclusion: These results suggest, in part, that the activity of HSP27 and MAPKs affect stressors, such as PDGF, AngII, TNF$\alpha$, $H_2O_2$, and starvation in rat smooth and skeletal muscles. However, more systemic research will be needed into physical therapy, including thermotherapy, electrotherapy, radiotherapy and others.

• Proceedings of the Korean Society of Plant Biotechnology Conference
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• 한국식물생명공학회 2005년도 추계학술대회 및 한일 식물생명공학 심포지엄
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• pp.168-168
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• 2005

• Korean journal of applied entomology
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• 제50권2호
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• pp.131-139
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• 2011

This study investigated the adverse effects of sound treatment on physiological processes of the American leafminer, Liriomyza trifolii, during several developmental stages. Larval feeding activity was analyzed by measuring feeding tunnel length. It was significantly suppressed by sound treatment (5,000 Hz, 95 dB). Sound treatment delayed the pupal period at 315 - 5,000 Hz and prevented adult emergence at 1,000 - 5,000 Hz. Female oviposition was also inhibited by the stress sound treatments. However, phototactic adult movement was not affected by sound treatment. Pupae treated with 5,000 Hz showed marked changes in protein patterns analyzed by two dimensional electrophoresis. MALDI-TOF analysis of specific protein spots indicated that trafficking protein particle complex I, triosephosphate isomerase, hypothetical protein TcasGA2_TC013388, polycystin-2, paraneoplastic neuronal antigen MA1, and tropomyosin I (isoform M) were predicted in the control insects and disappeared in the insects treated with sound. By contrast, DOCK9, cytoskeletal keratin II, and F0F1-ATP synthase beta subunit were predicted only in the sound-treated insects. Furthermore, stress sound significantly increased the susceptibility of L. trifolii to insecticides. These results suggest that physiological processes of L. trifolii are altered by sound stress, which may be exploited to develop a novel physical control tactic against L. trifolii.

• Proceedings of the Korean Society of Crop Science Conference
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• 한국작물학회 2017년도 9th Asian Crop Science Association conference
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• pp.127-127
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• 2017

Aluminum is the most abundant metallic element in the Earth's crust and considered as the most limiting factor for plant productivity in acidic soils. The inhibition of root growth is recognized as the primary effect of Al toxicity. Seeds of wheat cv. Keumkang (Korean cultivar) were germinated on petridish for 5 days and then transferred hydroponic apparatus which was treated with $0{\mu}M$ $AlCl_3$ (control), $100{\mu}M$ $AlCl_3$ and $150{\mu}M$ $AlCl_3$ for 5 days. The length of roots, shoots and fresh weight of wheat seedlings were decreased under aluminum stress. The concentrations of $K^+$, $Mg^{2+}$ and $Ac^{2+}$ were decreased whereas $Al^{3+}$ and $P_2O_5{^-}$ concentration was increased under aluminum stress. Using confocal microscopy, the fluorescence intensity of aluminum was increased with morin staining. In this study, a proteome analysis was performed to identify proteins, which is responsible to aluminum stress in wheat roots. In 10-day-old seedlings, proteins were extracted from roots and separated by 2-DE, stained by CBB. Using image analysis, a total of 47 differentially expressed protein spots were selected, whereas 19 protein spots were significantly up-regulated such as s-adenosylmethionine, oxalate oxidase, malate dehydrogenase, cysteine synthase, ascorbate peroxidase and 28 protein spots were significantly down-regulated such as heat shock protein 70, o-methytransferase 4, enolase, amylogenin by aluminum stress following protein spots analyzed by LTQ-FTICR mass spectrometry. The results provide the global picture of Al toxicity-induced alterations of protein profiles in wheat roots, and identify the Al toxicity-responsive proteins related to various biological processes that may provide some novel clues about plant Al tolerance.

• Development and Reproduction
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• 제21권4호
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• pp.407-415
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• 2017

In the present study, we investigated the role of binding immunoglobulin protein/glucose-regulated protein, 78-kDa (BIP/GRP78)-regulated endoplasmic reticulum (ER)-stress on meiotic maturation and cumulus cells expansion in porcine cumulus-oocyte complexes (COCs). Previously, it has been demonstrated that unfolded protein response (UPR)-related genes, such as molecules involved in ER-stress defense mechanisms, were expressed in matured oocytes and cumulus cells during in vitro maturation (IVM) of porcine oocytes. However, BIP/GRP78-mediated regulation of ER stress in porcine oocytes has not been reported. Firstly, we observed the effects of knockdown of BIP/GRP78 (an UPR initiation marker) using porcine-specific siRNAs (#909, #693, and #1570) on oocyte maturation. Among all siRNAs, siRNA #693 significantly reduced the protein levels of UPR marker proteins (BIP/GRP78, ATF4, and P90ATF6) in porcine COCs observed by Western blotting and immunofluorescence analysis. We also observed that the reduction of BIP/GRP78 levels by siRNA#693 significantly inhibited the meiotic maturation of oocytes (siRNA #693: $32.5{\pm}10.1%$ vs control: $77.8{\pm}5.3%$). In addition, we also checked the effect of ER-stress inhibitors, tauroursodeoxycholic acid (TUDCA, $200{\mu}M$) and melatonin ($0.1{\mu}M$), in BIP/GRP78-knockdown oocytes. TUDCA and melatonin treatment could restore the expression levels of ER-stress marker proteins (BIP/GRP78, $p-eIF2{\alpha}$, $eIF2{\alpha}$, ATF4, and P90ATF6) in siRNA #693-transfected matured COCs. In conclusion, these results demonstrated that BIP/GRP78-mediated regulation of UPR signaling and ER stress plays an important role in in vitro maturation of porcine oocytes.

• Proceedings of the Korean Society of Crop Science Conference
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• 한국작물학회 2017년도 9th Asian Crop Science Association conference
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• pp.124-124
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• 2017

Cadmium (Cd) is of particular concern because of its widespread occurrence and high toxicity and may cause serious morpho-physiological and molecular abnormalities in in plants. The present study was performed to explore Cd-induced morpho-physiological alterations and their potentiality associated mechanisms in Sorghum bicolor leaves at the protein level. Ten-day-old sorghum seedlings were exposed to different concentrations (0, 100, and $150{\mu}M$) of $CdCl_2$, and different morpho-physiological responses were recorded. The effects of Cd exposure on protein expression patterns in S. bicolor were investigated using two-dimensional gel electrophoresis (2-DE) in samples derived from the leaves of both control and Cd-treated seedlings. The observed morphological changes revealed that the plants treated with Cd displayed dramatically altered shoot lengths, fresh weights, and relative water content. In addition, the concentration of Cd was markedly increased by treatment with Cd, and the amount of Cd taken up by the shoots was significantly and directly correlated with the applied level of Cd. Using the 2-DE method, a total of 33 differentially expressed protein spots were analyzed using MALDI-TOF/TOF MS. Of these, treatment with Cd resulted in significant increases in 15 proteins and decreases in 18 proteins. Significant changes were absorbed in the levels of proteins known to be involved in carbohydrate metabolism, transcriptional regulation, translation and stress responses. Proteomic results revealed that Cd stress had an inhibitory effect on carbon fixation, ATP production and the regulation of protein synthesis. In addition, the up-regulation of glutathione S-transferase and cytochrome P450 may play a significant role in Cd-related toxicity and stress responses. Our study provides insights into the integrated molecular mechanisms involved in response to Cd and the effects of Cd on the growth and physiological characteristics of sorghum seedlings. The upregulation of these stress-related genes may be candidates for further research and use in genetic manipulation of sorghum tolerance to Cd stress.

• Asian-Australasian Journal of Animal Sciences
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• 제30권6호
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• pp.857-864
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• 2017

Objective: The purpose of this study was to investigate the influence of AMP-activated protein kinase (AMPK) activation on protein acetylation and glycolysis in postmortem muscle to better understand the mechanism by which AMPK regulates postmortem glycolysis and meat quality. Methods: A total of 32 mice were randomly assigned to four groups and intraperitoneally injected with 5-Aminoimidazole-4-carboxamide1-${\beta}$-D-ribofuranoside (AICAR, a specific activator of AMPK), AICAR and histone acetyltransferase inhibitor II, or AICAR, Trichostatin A (TSA, an inhibitor of histone deacetylase I and II) and Nicotinamide (NAM, an inhibitor of the Sirt family deacetylases). After mice were euthanized, the Longissimus dorsi muscle was collected at 0 h, 45 min, and 24 h postmortem. AMPK activity, protein acetylation and glycolysis in postmortem muscle were measured. Results: Activation of AMPK by AICAR significantly increased glycolysis in postmortem muscle. At the same time, it increased the total acetylated proteins in muscle 45 min postmortem. Inhibition of protein acetylation by histone acetyltransferase inhibitors reduced AMPK activation induced increase in the total acetylated proteins and glycolytic rate in muscle early postmortem, while histone deacetylase inhibitors further promoted protein acetylation and glycolysis. Several bands of proteins were detected to be differentially acetylated in muscle with different glycolytic rates. Conclusion: Protein acetylation plays an important regulatory role in postmortem glycolysis. As AMPK mediates the effects of pre-slaughter stress on postmortem glycolysis, protein acetylation is likely a mechanism by which antemortem stress influenced postmortem metabolism and meat quality though the exact mechanism is to be elucidated.

• The Korean Journal of Physiology and Pharmacology
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• 제28권5호
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• pp.435-447
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• 2024

Secretory proteins, including plasma membrane proteins, are generally known to be transported to the plasma membrane through the endoplasmic reticulum-to-Golgi pathway. However, recent studies have revealed that several plasma membrane proteins and cytosolic proteins lacking a signal peptide are released via an unconventional protein secretion (UcPS) route, bypassing the Golgi during their journey to the cell surface. For instance, transmembrane proteins such as the misfolded cystic fibrosis transmembrane conductance regulator (CFTR) protein and the Spike protein of coronaviruses have been observed to reach the cell surface through a UcPS pathway under cell stress conditions. Nevertheless, the precise mechanisms of the UcPS pathway, particularly the molecular machineries involving cytosolic motor proteins, remain largely unknown. In this study, we identified specific kinesins, namely KIF1A and KIF5A, along with cytoplasmic dynein, as critical players in the unconventional trafficking of CFTR and the SARS-CoV-2 Spike protein. Gene silencing results demonstrated that knockdown of KIF1A, KIF5A, and the KIF-associated adaptor protein SKIP, FYCO1 significantly reduced the UcPS of △F508-CFTR. Moreover, gene silencing of these motor proteins impeded the UcPS of the SARS-CoV-2 Spike protein. However, the same gene silencing did not affect the conventional Golgi-mediated cell surface trafficking of wild-type CFTR and Spike protein. These findings suggest that specific motor proteins, distinct from those involved in conventional trafficking, are implicated in the stress-induced UcPS of transmembrane proteins.

• Journal of the Korean Society of Food Science and Nutrition
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• 제44권4호
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• pp.475-482
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• 2015

This study was conducted to examine whether or not oligonol, a low molecular weight polyphenol derived from lychee fruit, has an ameliorative effect on diabetes-induced oxidative stress-related hepatic damage in streptozotocin (STZ)-induced diabetic rats. Oligonol (10 or 20 mg/kg body weight; O10 or O20, respectively) was orally administered every day for 10 days to STZ-induced diabetic rats, and its effects were compared to vehicle-treated diabetic (Veh) and non-diabetic rats. Administration of 20 mg/kg of oligonol significantly decreased liver weight compared with the Veh group (P<0.05). Elevated levels of hepatic glucose, reactive oxygen species, peroxynitrite, and lipid peroxidation were detected in diabetic vehicle rats, whereas oligonol treatment significantly attenuated these levels (P<0.05). In diabetic vehicle rats, hepatic antioxidant enzyme protein levels decreased, whereas oligonol treatment showed significant elevated results. For inflammation-related protein expression, oligonol-treated groups showed insignificant reduction. Oligonol improved expression of proapoptotic protein caspase-3 in the liver of diabetic rats (P<0.05). In conclusion, these results provide important evidence that oligonol exhibits an inhibitory effect on oxidative stress and apoptosis-related protein expression as well as a hepato-protective effect against the development of diabetic complications in STZ-induced type 1 diabetic rats.