• International Journal of Oral Biology
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• 제45권4호
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• pp.169-178
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• 2020

L-ascorbic acid (L-AA; vitamin C) induces apoptosis in cancer cells. This study aimed to elucidate the molecular mechanisms of L-AA-induced apoptosis in human laryngeal epidermoid carcinoma Hep-2 cells. L-AA suppressed the viability of Hep-2 cells and induced apoptosis, as shown by the cleavage and condensation of nuclear chromatin and increased number of Annexin V-positive cells. L-AA decreased Bcl-2 protein expression but upregulated Bax protein levels. In addition, cytochrome c release from the mitochondria into the cytosol and activation of caspase-9, -8, and -3 were enhanced by L-AA treatment. Furthermore, apoptosis-inducing factor (AIF) and endonuclease G (EndoG) were translocated into the nucleus during apoptosis of L-AA-treated Hep-2 cells. L-AA effectively inhibited the constitutive nuclear factor-κB (NF-κB) activation and attenuated the nuclear expression of the p65 subunit of NF-κB. Interestingly, L-AA treatment of Hep-2 cells markedly activated Akt and mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase [JNK]) and and LY294002 (Akt inhibitor), SB203580 (p38 inhibitor) or SP600125 (a JNK inhibitor) decreased the levels of Annexin V-positive cells. These results suggested that L-AA induces the apoptosis of Hep-2 cells via the nuclear translocation of AIF and EndoG by modulating the Bcl-2 family and MAPK/Akt signaling pathways.

• The Korean Journal of Physiology and Pharmacology
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• 제26권2호
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• pp.87-94
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• 2022

Myocardial infarction promotes cardiac remodeling and myocardial fibrosis, thus leading to cardiac dysfunction or heart failure. Peiminine has been regarded as a traditional anti-fibrotic Chinese medicine in pulmonary fibrosis. However, the role of peiminine in myocardial infarction-induced myocardial injury and fibrosis remained elusive. Firstly, rat model of myocardial infarction was established using ligation of the left coronary artery, which were then intraperitoneally injected with 2 or 5 mg/kg peiminine once a day for 4 weeks. Echocardiography and haemodynamic evaluation results showed that peiminine treatment reduced left ventricular end-diastolic pressure, and enhanced maximum rate of increase/decrease of left ventricle pressure (± dP/dt max) and left ventricular systolic pressure, which ameliorate the cardiac function. Secondly, myocardial infarction-induced myocardial injury and infarct size were also attenuated by peiminine. Moreover, peiminine inhibited myocardial infarction-induced increase of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α production, as well as the myocardial cell apoptosis, in the rats. Thirdly, peiminine also decreased the myocardial fibrosis related protein expression including collagen I and collagen III. Lastly, peiminine reduced the expression of p38 and phosphorylation of extracellular signal-regulated kinase 1/2 in rat model of myocardial infarction. In conclusion, peiminine has a cardioprotective effect against myocardial infarction-induced myocardial injury and fibrosis, which can be attributed to the inactivation of mitogen-activated protein kinase pathway.

• Journal of Applied Biological Chemistry
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• 제65권1호
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• pp.33-41
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• 2022

Esculetin (also known as 6, 7-dihydroxycoumarin) a type of coumarin, has been exhibited anti-inflammatory and anti-aging effects. Biorenovation is the microbe-mediated enhancement of biological efficacies and structurally diversified compounds relative to their substrate compounds. The production of different kinds of esculetin derivatives using Bacillus sp. JD3-7 and their effects on lipopolysaccharide (LPS)-triggered inflammatory response in RAW 26.7 cells were assessed. One of the biorenovation products, identified as esculetin 6-O-phosphate (ESP), at concentrations of 1.25, 2.5, and 5 μM inhibited the LPS-stimulated production of inflammation markers of nitric oxide synthase 2 and cyclooxygenase 2 as well as their respective enzymatic reaction products of nitric oxide and prostaglandin E2 in the order of increasing concentrations (1.25, 2.5, and 5 μM). Additionally, ESP treatment suppressed the LPS-stimulated secretion of pro-inflammatory cytokines of interleukin (IL)-1β, IL-6, and tumor necrosis factor- α. Furthermore, these anti-inflammatory effect of ESP was associated with the downregulation of mitogen-activated protein kinase signaling, that is, extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase signaling pathways. This study would therefore provide interesting insights into the biorenovation-assisted generation of a novel anti-inflammatory compound. ESP may be used to develop treatments for inflammatory disorders.

• Asian-Australasian Journal of Animal Sciences
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• 제20권6호
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• pp.954-961
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• 2007

The experiments were conducted to determine effects of a mixture of conjugated linoleic acid (CLA) isomers on T cell subpopulations and responsiveness to mitogen of splenocytes in male broiler chicks. In experiment 1, birds (8-d old) were fed basal, CLA-(CLA) and safflower oil-supplemented (SA) diets which were formulated by supplementary 10 g CLA or safflower oil/kg to the basal diet for 14 d. Broiler starter diet, which mainly consisted of corn and soybean meal, was served as the basal diet. Proliferative response and interleukin (IL)-2-like activity stimulated by concanavalin (Con) A at a concentration of $10{\mu}g/ml$ of splenocytes in chicks fed the CLA diet were greater than in chicks fed the SA diet, but not at $20{\mu}g$ Con A/ml. Percentage of CD3-positive T cells in splenocytes did not differ between chicks fed the SA diet and CLA. Ratio of CD4-positive T cells to CD8- positive T cells was significantly affected by dietary fat source. In experiment 2, broiler chicks (1-d old) were fed the same diets as in experiment 1 for 14 d. Results of splenocyte proliferation to Con A were similar to those in experiment 1, but phytohemaggulutinin (PHA)- or pokeweed mitogen (PWM)- induced splenocyte proliferation did not differ between the CLA and SA fed groups. Supplementation with SA or CLA to the basal diet tended to have a depressive effect on the proliferation, with the greater effect being that of SA. In experiment 3, effect of an addition of CLA to splenocyte culture medium on splenocyte proliferation was determined. An addition of CLA to the culture medium resulted in reduction of the splenocyte proliferation to Con A, but an addition of linoleic acid. When PWM and PHA were used as mitogen, the inhibitory effect of CLA and linoleic acid on the proliferation did not differ. The results suggested that the effect of dietary CLA on splenocyte proliferation was similar to that of SA, although the effect of dietary CLA on sub-populations was slightly different from that of dietary SA. Further studies are needed to clarify whether use of CLA would be beneficial for maintaining or enhancing T cell immunity in chicks.

• Journal of Korean Neurosurgical Society
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• 제46권4호
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• pp.389-396
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• 2009

Objective : Triptolide (TP) has been reported to suppress the expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), of which main function is to inactivate the extracellular signal-regulated kinase-1/2 (ERK-1/2), the p38 MAPK and the c-Jun N-terminal kinase-1/2 (JNK-1/2), and to exert antiproliferative and pro-apoptotic activities. However, the mechanisms underlying antiproliferative and pro-apoptotic activities of TP are not fully understood. The purpose of this study was to examine whether the down-regulation of MKP-1 expression by TP would account for antiproliferative activity of TP in immortalized HT22 hippocampal cells. Methods : MKP-1 expression and MAPK phosphorylation were analyzed by Western blot. Cell proliferation was assessed by $^3H$-thymidine incorporation. Small interfering RNA (siRNA) against MKP-1, vanadate (a phosphatase inhibitor), U0126 (a specific inhibitor for ERK-1/2), SB203580 (a specific inhibitor for p38 MAPK), and SP600125 (a specific inhibitor for JNK-1/2) were employed to evaluate a possible mechanism of antiproliferative action of TP. Results : At its non-cytotoxic dose, TP suppressed MKP-1 expression, reduced cell growth, and induced persistent ERK-1/2 activation. Similar growth inhibition and ERK-1/2 activation were observed when MKP-1 expression was blocked by MKP-1 siRNA and its activity was inhibited by vanadate. The antiproliferative effects of TP, MKP-1 siRNA, and vanadate were significantly abolished by U0126, but not by SB203580 or SP600125. Conclusion : Our findings suggest that TP inhibits the growth of immortalized HT22 hippocampal cells via persistent ERK-1/2 activation by suppressing MKP-1 expression. Additionally, this study provides evidence supporting that MKP-1 may play an important role in regulation of neuronal cell growth.

• 한국가금학회지
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• 제34권1호
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• pp.31-36
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• 2007

비태인이 산란계의 면역 반응에 어떠한 영향을 미치는지 알아보기 위하여 in vitro와 in vivo 시험을 시행하였다. 처리구당 18수씩 총 72수를 공시하였고, 비태인 0, 300, 600, 1,200 ppm 수준으로 산란계 사료에 첨가 급여하였다. 시험결과, in vitro 시험에서 비장 림프구 증식은 비태인 만을 처리하였을 때에는 증식 반응은 일어나지 않았으나 Con A와 PWM을 처리하였을 때 증식 반응은 현저하게 증가하였다. 또한 Con A만을 처리했을 때보다 Con A와 비태인을 동시에 처리했을 때 반응성이 현저하게 증가하였다. 그러나 PWM과 비태인을 동시에 처리했을 때는 PWM만을 처리했을 때와 비교해서 차이를 보이지 않았다. 사료에 비태인을 첨가 급여한 in vivo시험에서 Con A의 자극에 대한 비장 림프구 증식반응은 비태인의 첨가 수준에 따라 증가하는 경향을 보였으나 1,200 ppm 급여구에서는 대조구에 비하여 감소하는 경향을 보였다. 이러한 경향은 Con A와 함께 비태인(0.1 mM)을 처리했을 때도 동일하게 나타났다. PWM의 자극에 대한 반응은 Con A에 비하여 약하게 나타났으며 비태인 급여 수준에 따른 차이도 적게 나타났다. 비태인을 급여한 산란계 비장의 무게에서 처리구간에 통계적인 차이는 없었다. 비태인 첨가구는 대조구에 비하여 전체적으로 증가하는 경향을 보였고, 비태인 300 ppm 첨가구가 가장 높은 수치를 나타내었다. 비태인을 수준별로 급여하여 SRBC 항체가를 조사한 결과에서도 처리구간 유의적인 차이는 나타나지 않았다. 따라서 본 시험의 결과, 비태인의 처리는 in vivo 상에서 Con A로 비장 림프구의 증식을 유도한 경우 유의하게 비장 림프구의 증식을 증가시켰다.

• Korean Journal of Acupuncture
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• 제31권1호
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• pp.14-19
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• 2014

목적 : 본 연구에서는 정향 에탄올 추출물이 RBL-2H3 세포 매개 알레르기 반응에 대해 미치는 영향과 그 작용기전에 대해 연구했다. 방법 : 정향 에탄올 추출물의 RBL-2H3 세포에 대한 독성 여부는 MTT 분석을 통해 평가했다. 정향 에탄올 추출물의 항알러지 작용은 효소결합면역 분석방법(ELISA)을 이용해 ${\beta}$-Hexosaminidase과 Histamine의 분비량을 측정하여 평가하였다. 정향 에탄올 추출물의 작용기전에 대해서는 유사 분열물질-활성화단백질인산화효소(mitogen-activated protein kinase, MAPK)를 western blot 법을 이용하여 측정함으로써 평가하였다. 결과 : 정향의 에탄올 추출물은 RBL-2H3 세포에 대해 독성을 나타내지 않는 농도에서 RBL-2H3 세포의 탈과립과 히스타민 분비를 유의하게 억제하였으며, p38 MAPK의 활성을 차단하였다. 결론 : 본 연구의 결과 정향의 에탄올 추출물은 비만세포에서 유래된 알러지 반응을 억제하는 효과가 있으며, 또한 그 작용기전은 p38 MAPK 인산화와 연계되어 있을 것으로 사료된다.

• Parasites, Hosts and Diseases
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• 제25권1호
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• pp.1-6
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• 1987

N. fowleri를 감염시키고 그 경과에 따른 숙주의 면역기능 변동을 알아보고자 마우스에 N. fowleri를 감염시키고 그 경과에 따른 T임파구 기능과 혈청내 항체가를 관찰하였다. T임파구 기능을 알아보기 위하여 비장세포를 배양할 때 mitogen으로 con. A와 N. fowleri lysate를 첨가하고 42시간 배양후 $methyl-[^3H]-thymidine$을 넣어 비장세포에 uptake되는 정도를 측정하였으며 혈청내 항체가는 효소표식 면역검사법(ELISA)으로 측정하였다. 실험성적을 요약하면 다음과 같다. T임파구의 기능은 사용된 mitogen con. A와 N. fowleri lysated에 관계없이 감염 후 3일부터 감소되어 11일까지 대조군에 비해 유의하게 감소하였다. 감염후 15일에는 N. fowleri lysate를 사용하였을 경우 T임파구 기능이 계속 감소되어 있었으나 con. A를 첨가하였을때 정상대조군과 차이가 없음을 알 수 있었다.

• 한국동물학회:학술대회논문집
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• 한국동물학회 1998년도 한국생물과학협회 학술발표대회
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• pp.303.1-303
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• 1998

No Abstract, See Full Text

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.191-191
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• 2002