• Archives of Pharmacal Research
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• 제27권3호
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• pp.324-333
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• 2004

To determine whether Insulin-like growth factor (IGF-I) treatment represents a potential means of enhancing the survival of cardiac muscle cells from adriamycin (ADR)-induced cell death, the present study examined the ability of IGF-I to prevent cell death. The study was performed utilising the embryonic, rat, cardiac muscle cell line, H9C2. Incubating cardiac muscle cells in the presence of adriamycin increased cell death, as determined by MTT assay and annexin V-positive cell number. The addition of 100 ng/mL IGF-I, in the presence of adriamycin, decreased apoptosis. The effect of IGF-I on phosphorylation of PI, a substrate of phosphatidylinositol 3-kinase (PI 3-kinase) or protein kinase B (AKT), was also examined in H9C2 cardiac muscle cells. IGF-I increased the phosphorylation of ERK 1 and 2 and $PKC{\;}{\zeta}{\;}kinase$. The use of inhibitors of PI 3-kinase (LY 294002), in the cell death assay, demonstrated partial abrogation of the protective effect of IGF-I. The MEK1 inhibitor-PD098059 and the PKC inhibitor-chelerythrine exhibited no effect on IGF-1-induced cell protection. In the regulatory subunit of PI3K-p85- dominant, negative plasmid-transfected cells, the IGF-1-induced protective effect was reversed. This data demonstrates that IGF-I protects cardiac muscle cells from ADR-induced cell death. Although IGF-I activates several signaling pathways that contribute to its protective effect in other cell types, only activation of PI 3-kinase contributes to this effect in H9C2 cardiac muscle cells.

• 대한한방내과학회지
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• 제26권2호
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• pp.420-430
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• 2005

The water extract of Omijatang(OMJT) has been traditionally used for treatment of abscess and heart palpitation in oriental medicine, However, little is known about the mechanism by which the water extract of OMJT rescues cells from these damages. This study was designed to investigate the protective mechanisms of OMJT in H9c2 cardiomyoblasts on oxidative stress-induced cytotoxicity including $H_2O_2,\;ZnCl_2$, hypoxia, and reoxygenation. Oxidative stress markedly decreased the viability of H9c2 cells. This was characterized with apparent apoptotic features such as chromatin condensation as well as fragmentation of genomic DNA and nuclei. However, OMJT significantly reduced $H_2O_2$-induced cell death and apoptotic characteristics as well as $ZnCl_2$, hypoxialreoxygenation. Taken together, this study suggests that the water extract of OMJT has the protective effects against oxidative injuries.

• The Korean Journal of Physiology and Pharmacology
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• 제23권1호
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• pp.37-45
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• 2019

To study the effect of nicorandil pretreatment on ketone body metabolism and Acetyl-CoA acetyltransferase (ACAT1) activity in hypoxia/reoxygenation (H/R)-induced cardiomyocytes. In our study, we applied H9c2 cardiomyocytes cell line to evaluate the cardioprotective effects of nicorandil. We detected mitochondrial viability, cellular apoptosis, reactive oxygen species (ROS) production and calcium overloading in H9c2 cells that exposed to H/R-induced cytotoxicity. Then we evaluated whether nicorandil possibly regulated ketone body, mainly ${\beta}$-hydroxybutyrate (BHB) and acetoacetate (ACAC), metabolism by regulating ACAT1 and Succinyl-CoA:3-ketoacid coenzyme A transferase 1 (OXCT1) protein and gene expressions. Nicorandil protected H9c2 cardiomyocytes against H/R-induced cytotoxicity dose-dependently by mitochondria-mediated anti-apoptosis pathway. Nicorandil significantly decreased cellular apoptotic rate and enhanced the ratio of Bcl-2/Bax expressions. Further, nicorandil decreased the production of ROS and alleviated calcium overloading in H/R-induced H9c2 cells. In crucial, nicorandil upregulated ACAT1 and OXCT1 protein expressions and either of their gene expressions, contributing to increased production of cellular BHB and ACAC. Nicorandil alleviated cardiomyocytes H/R-induced cytotoxicity through upregulating ACAT1/OXCT1 activity and ketone body metabolism, which might be a potential mechanism for emerging study of nicorandil and other $K_{ATP}$ channel openers.

• Biomolecules & Therapeutics
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• 제21권5호
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• pp.358-363
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• 2013

In the present study, we investigated the effect of intracellular glutathione (GSH) depletion in heart-derived H9c2 cells and its mechanism. L-buthionine-S,R-sulfoximine (BSO) induced the depletion of cellular GSH, and BSO-induced reactive oxygen species (ROS) production was inhibited by glutathione monoethyl ester (GME). Additionally, GME inhibited BSO-induced caspase-3 activation, annexin V-positive cells, and annexin V-negative/propidium iodide (PI)-positive cells. Treatment with rottlerin completely blocked BSO-induced cell death and ROS generation. BSO-induced GSH depletion caused a translocation of PKC-${\delta}$ from the cytosol to the membrane fraction, which was inhibited by treatment with GME. From these results, it is suggested that BSO-induced depletion of cellular GSH causes an activation of PKC-${\delta}$ and, subsequently, generation of ROS, thereby inducing H9c2 cell death.

• 대한의생명과학회지
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• 제9권3호
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• pp.145-150
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• 2003

In the intestinal mucosa, mast cells are thought to be responsible for the expulsion of parasites. We investigated the relationship of worm expulsion and mast cells in C3H/HeN and BALB/c mice infected with Echinostoma hortense. In addition, we examined whether the worm recovery rate was associated with the strain of mice, and whether a toluidine stain and immunohistochemistry using the c-kit antibody was effective in the detection of mast cells. In order to investigate the mucosal immune response of C3H/HeN and BALB/c mice, each mouse was infected orally with 30 E. hortense metacercariae. Then, the number of mucosal mast cells and worm recovery rates was observed in experimentally infected mouse strains between 1 week and 8 weeks post infection (PI). Mucosal mast cells were increased in 3 weeks P.I. in C3H/HeN and BALB/c mice. On the other hand, only mucosal goblet cells and worm recovery rates correlated in C3H/HeN mice (P=0.0482). Worm recoveries in C3H/HeN mice were 65.7$\pm$5.6, 53.3$\pm$5.4 and 6.7$\pm$0.6 in week 1, 2, and 3 P.I. and strongly decreased in week 3 P.I. Worm recoveries in BALB/c mice were 23.0$\pm$2.5, 10.0$\pm$1.0, and 6.7$\pm$0.6% in week 1, 2, and 3 P.I. and gradually decreased from week 1 P.I. to week 3 P.I. Worm recoveries in C3H/HeN mice were significantly higher than in BALB/c mice (P<0.00l). The number of mast cells in C3H/HeN and BALB/c mice using the anti-c-kit antibody reached to a peak in week 3 P.I. and recovered as normal level in week 5 P.I. and 6 P.I. The number in E. hortense-infected C3H/HeN mice (P=0.0015) was higher than in E. hortense-infected BALB/c mice (P=0.01) compared with the control group. There were significant differences in the number of mast cells among regions of the intestine in in C3H/HeN mice (P<0.05) but not in BALB/c mice (P>0.05). Immunohistochemistry using the anti-c-kit antibody was significant method as an examination of the number of mast cells (P=0.0002). In conclusion, the present study demonstrated that mast cells play an important role in worm recovery, and immunohistochemistry using the anti-c-kit antibody was superior to toluidine stain as an examination of mast cells.

• 한국식품저장유통학회지
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• 제31권2호
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• pp.298-306
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• 2024

본 연구에서는 식물 추출물 혼합 분말의 근육세포 분화 및 산화적 스트레스에 대한 세포 보호 효과를 확인하고자 하였다. 추출물을 최대 1,000 ㎍/mL 농도까지 세포에 처리한 결과, 세포 생존율이 감소하지 않음을 확인되었다. 식물 추출물 혼합분말이 근육세포 분화 인자에 미치는 영향을 확인하기 위해 myogenin과 MHC의 발현 여부를 확인한 결과, 무처리군에 비해 발현이 증가함을 확인하였다. H₂O₂에 의해 유도된 산화적 스트레스에 대한 세포 보호 효과를 확인한 결과, 식물 추출물 혼합 분말 처리에 의해 H₂O₂ 단독 처리군보다 세포 생존율이 증가하였으며, LDH와 creatine kinase의 활성이 감소하였다. 또한, Bax와 Bcl-2의 발현을 조절하여 caspase-9와 -3 활성화를 억제함을 확인하였다. 이를 통해 식물 추출물 혼합 분말의 근육세포 분화 효과 및 H₂O₂에 의해 유도된 산화적 스트레스에 대한 세포 보호 효과가 있음을 확인하였다. 따라서 식물 추출물 혼합 분말은 근감소증 개선을 위한 기능성 소재로써 활용이 가능할 것으로 판단되며, 향후 근감소증 개선을 위한 기능성 소재로서의 유효성 확보를 위해서 근감소증 세포 및 동물모델을 이용한 효능 및 기전 분석 연구가 더 필요할 것으로 사료된다.

• BMB Reports
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• 제50권9호
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• pp.435-436
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• 2017

Primed human pluripotent stem cells (hPSCs) are highly dependent on glycolysis rather than oxidative phosphorylation, which is similar to the metabolic switch that occurs in cancer cells. However, the molecular mechanisms that underlie this metabolic reprogramming in hPSCs and its relevance to pluripotency remain unclear. Cha et al. (2017) recently revealed that downregulation of SIRT2 by miR-200c enhances acetylation of glycolytic enzymes and glycolysis, which in turn facilitates cellular reprogramming, suggesting that SIRT2 is a key enzyme linking the metabolic switch and pluripotency in hPSCs.

• Journal of Ginseng Research
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• 제44권2호
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• pp.258-266
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• 2020

Background: Oxidative stress-induced cardiomyocytes apoptosis is a key pathological process in ischemic heart disease. Glutathione reductase (GR) reduces glutathione disulfide to glutathione (GSH) to alleviate oxidative stress. Ginsenoside Rb1 (GRb1) prevents the apoptosis of cardiomyocytes; however, the role of GR in this process is unclear. Therefore, the effects of GRb1 on GR were investigated in this study. Methods: The antiapoptotic effects of GRb1 were evaluated in H9C2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, annexin V/propidium iodide staining, and Western blotting. The antioxidative effects were measured by a reactive oxygen species assay, and GSH levels and GR activity were examined in the presence and absence of the GR inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular docking and molecular dynamics simulations were used to investigate the binding of GRb1 to GR. The direct influence of GRb1 on GR was confirmed by recombinant human GR protein. Results: GRb1 pretreatment caused dose-dependent inhibition of tert-butyl hydroperoxide-induced cell apoptosis, at a level comparable to that of the positive control N-acetyl-L-cysteine. The binding energy between GRb1 and GR was positive (-6.426 kcal/mol), and the binding was stable. GRb1 significantl reduced reactive oxygen species production and increased GSH level and GR activity without altering GR protein expression in H9C2 cells. Moreover, GRb1 enhanced the recombinant human GR protein activity in vitro, with a half-maximal effective concentration of ≈2.317 μM. Conversely, 1,3-bis-(2-chloroethyl)-1-nitrosourea co-treatment significantly abolished the GRb1's apoptotic and antioxidative effects of GRb1 in H9C2 cells. Conclusion: GRb1 is a potential natural GR agonist that protects against oxidative stress-induced apoptosis of H9C2 cells.

• 한국식품영양과학회지
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• 제29권2호
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• pp.235-240
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• 2000

Inhibitory effects of cockle extracts on carcinogen-induced cytotoxicity in C3H/10T1/2 cells were studied. Soup (62$\mu\textrm{g}$/mL), solubility (28$\mu\textrm{g}$/mL) and liposolubility (9 $\mu\textrm{g}$/mL) of the cockle inhibited 3-methyl-cholanthrene(MCA)-induced cytotoxicity in C3H/10T1/2 cells by 53 and 94%, respectively. These results suggest that the extracts cockle might have anticarcinogen-induced cytotoxicity of C3H/10T1/2 cells. The effects of cockle extracts on the immune response related to its antitumor activity in vitro and in vivo were investigated. The cockle extracts showed a direct cytotoxic effect on sarcoma-180 cells, tumor cells in vitro. Soup (0.49 mg/mL), solubility (0.11 mg/mL) and liposolubiliy (0.05 mg/mL) of the cockle markedly decreased the total numbers of sarcoma-180 cells, but not their viability. The phagocytic acitivity of peritoneal macrophage of mice was significantly augmented by these extracts of the cockle compared with that of control in vivo. These extracts also raised the phagocuytic index, indicating that the number of phagocytize dmicrobes per macrophage increased. Thus, cockle extracts might show a antitumor activity by enhancing the phagocytic cell activities.

• 태양에너지
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• 제5권2호
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• pp.46-53
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• 1985

Hydrogenated amorphous silicon solar cells which are fabricated by photo-chemical vapor deposition (photo-CVD) system has been investigated. In the photo-CVD system which consists of three separate reaction chambers, low-pressure mercury lamp has been used as a light source. The main reactant ($Si_2H_6/He$) gases which are premixed with a small amount of mercury vapor in a mercury-vaporizer kept at $50^{\circ}C$ have been used. Using $C_2H_2$ and $SiH_2(CH_3)_2$ as the carbon source, p-type wide band gap a-SiC:H films have been obtained. The result has been found that the undoped layers of the pin/substrate solar cells are influenced by the residual impurities, such as phosphorus and boron during the deposition process. By minimizing the effect of the impurities in the i-layer and optimizing conditions at the p-layer and p/i interface, the energy conversion efficiency of 9.61 % under AM-1 ($100mW/Cm^2$) has been achieved for pin/substrate solar cells illuminated through their p-layers, using the three separate reaction chamber apparatus. It is expected that a-SiC:H solar cells with the energy conversion efficiency over 10% have been fabricated by Photo-CVD method.