• Animal cells and systems
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• 제6권2호
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• pp.171-180
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• 2002

Nitric oxide has high affinity for iron, and thus it can cause intracellular iron loss. We tested the idea that intracellular iron can be the primary target of NO toxicity by comparing the signaling mechanisms involved in cell death caused by iron depletion and that caused by NO. Treatment of HL-60 cells with a NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), decreased the intracellular iron level rapidly as that observed with the iron chelator deferoxamine (DFO). Iron chelators such as DFO and mimosine could induce death of human leukemic HL-60 cells by a mechanism requiring activation of p38 kinase, c-Jun N-terminal kinase, caspase-3 and caspase-8. DFO and SNAP also caused release of cytochrome c from mitochondria. Inhibition of p38 kinase by a selective inhibitor, SB203580, abolished the NO and DFO-induced cell death, release of cytochrome c, and activation of caspase-3 and caspase-8, thus indicating that p38 kinase lies upstream in the cell death processes. In a parallel situation, the cells that are sensitive to NO showed similar sensitivity to DFO. Moreover, simultaneous addition of ferric citrate, an iron-containing compound, inhibited the SNAP and DFO-induced activation of caspases and also blocked the NO-mediated cell cycle arrest at $G_1$ phase. Collectively, our data implicate that the NO-induced cell death of tumor cells including HL-60 cells is mediated by depletion of iron and further suggest that activation of p38 kinase lies upstream of cytochrome c release and caspase activation involved in this apoptotic process.

• The Korean Journal of Physiology and Pharmacology
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• 제6권6호
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• pp.319-325
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• 2002

The induction of interleukin-6 (IL-6) using combined proinflammatory agents $(LPS/IFN-{\gamma}\;or\;TNF-{\alpha}/IFN-{\gamma})$ was studied in relation to p38 mitogen-activated protein kinase (MAPK) and $NF-{\kappa}B$ transcriptional factor in primary neonatal cardiomyocytes. When added to cultures of cardiomyocytes, the combined agents $(LPS/IFN-[\gamma}\;or\;TNF-{\alpha}/IFN-{\gamma})$ had stimulatory effect on the production of IL-6 and the elevation was significantly reduced by SB203580, a specific p38 MAPK inhibitor. SB203580 inhibited protein production and gene expression of IL-6 in a concentration-dependent manner. In this study, $IFN-{\gamma}$ enhancement of $TNF-{\alpha}-induced\;NF-{\kappa}B$ binding affinity as well as p38 MAP kinase activation was observed. However, a specific inhibitor of p38 MAPK, SB203580, had no effect on $TNF-{\alpha}/IFN-{\gamma}\;or\;LPS/IFN-{\gamma}-induced\;NF-{\kappa}B$ activation. This study strongly suggests that these pathways about $TNF-{\alpha}/IFN-{\gamma}$ or $LPS/IFN-{\gamma}-activated$ IL-6 release can be primarily dissociated in primary neonatal cardiomyocytes.

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2008년도 제49회 학술심포지움 및 국제학술대회
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• pp.38.1-38.1
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• 2008

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2001년도 학술 발표회 진행표 및 논문초록
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• pp.24-24
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• 2001

The present study was undertaken to determine whether p38 mitogen-activated protein kinase participates in the regulation of vascular smooth muscle contraction by endothelin-I (ET-1) in rat thoracic aorta. ET-1 induced a sustained contraction. In contrast, both the intracellular Ca$\^$2＋/ and myosin light chain (MLC) phosphorylations were not sustained.(omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.117.1-117.1
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• 2003

We investigated whether experimental esophagitis and IL-1$\beta$ could induce the activation of MAP kinases in esophageal smooth muscle. With two models of experimental esophagitis, we assessed the activity of p38 MAP kinase, p44/42 MAP kinase and JNK. In feline acute experimental esophagitis, immunoblotting of normal and esophagitis-induced smooth muscle with each types of MAP kinase antibodies revealed the slight increase of phosphorylated form of p38 MAP kinase, especially in membrane fraction. (omitted)

• 생명과학회지
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• 제27권1호
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• pp.8-14
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• 2017

치자 열매는 아시아에서 음식과 옷의 염료로 사용되어 왔다. 본 연구에서는 BV-2 소교세포에서 치자열매 열수추출물(GJ)의 항염증 효과를 관찰하고 그 작용 기전을 연구하였다. GJ는 세포에 독성을 유도하지 않으면서 lipopolysaccharide로 인한 nitric oxide (NO) 분비와 inducible nitric oxide synthase (iNOS) 생성 및 활성산소 생성을 억제하였다. 또한 GJ는 농도의존적으로 heme oxygenase-1 (HO-1)의 발현을 유도하였다. 더군다나 HO-1 siRNA를 처리했을 때는 GJ가 iNOS의 발현을 억제하지 못하였다. GJ는 HO-1의 발현에 관여하는 전사인자인 nuclear factor E2-related factor 2를 핵으로 이동시켰다. 또한 GJ에 의한 HO-1의 발현은 phosphatidylinositol 3-kinase(PI-3K) 및 p38 kinase 억제제에 의해 감소되었으며, GJ가 Akt와 p38 kinase의 인산화를 유도하였다. 이상의 결과를 종합해보면, GJ는 PI3K/Akt 및 p38 신호전달과정을 통해 HO-1의 발현을 유도함으로써 NO와 같은 염증매개물질의 생성을 억제한다는 것을 알 수 있다. 이러한 연구결과는 치자열매가 신경염증을 억제하는 새로운 기전을 밝힌 것이다.

• The Journal of Korean Physical Therapy
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• 제20권3호
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• pp.53-59
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• 2008

Purpose: The non-receptor-type protein tyrosine kinase Syk (636 amino acids, 72 kDa) is ubiquitously expressed in hematopoietic stem cells and has been widely studied as a regulator and effector of B cell receptor signaling that occurs in processes such as differentiation, proliferation and apoptosis. However, the mechanism relating Syk and p38 mitogen-activated protein kinases (p38MAPK) by endothelin-1 (ET-1, 21 amino acids) stimulation in muscle cells, especially in the volume-dependent hypertensive state, remains unclear. Methods: In this study, we investigated the relationship between Syk and p38MAPK for isometric contraction and enzymatic activity by ET-1 from rat aortic smooth muscle cells and aldosterone-analogue deoxycorticosterone acetate (DOCA) hypertensive state rats (ADHR). Results: The systolic blood pressure was significantly increased in ADHR than in a control group of animals. ET-1 induced isometric contraction and phosphorylation of p38MAPK, which was increased in muscle strips from ADHR. Increased vasoconstriction and phosphorylation of p38MAPK induced by treatment with 30 nM ET-1 were inhibited by the use of 10${\mu}M$ SB203580, an inhibitor of p38MAPK from ADHR. Furthermore, ET-1 induced isometric contraction and phosphorylation of Syk and p38MAPK, which were increased in the aortic smooth muscle cells. Increased tension and phosphorylation of Syk and p38MAPK induced by ET-1 were inhibited by SB203580 from rat aortic smooth muscle cells. Conclusion: These results, suggest that the Syk activity affects ET-1-induced contraction through p38MAPK in smooth muscle cells and that the same pathway directly or indirectly is associated with volume dependent hypertension. The findings suggest the need to develop cardiovascular disease-specialized physical therapy.

• Journal of Korean Neurosurgical Society
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• 제56권1호
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• pp.1-4
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• 2014

Objective : The aims of our study are to evaluate the effect of curcumin on spinal cord neural progenitor cell (SC-NPC) proliferation and to clarify the mechanisms of mitogen-activated protein (MAP) kinase signaling pathways in SC-NPCs. Methods : We established cultures of SC-NPCs, extracted from the spinal cord of Sprague-Dawley rats weighing 250 g to 350 g. We measured proliferation rates of SC-NPCs after curcumin treatment at different dosage. The immuno-blotting method was used to evaluate the MAP kinase signaling protein that contains extracellular signal-regulated kinases (ERKs), p38, c-Jun $NH_2$-terminal kinases (JNKs) and ${\beta}$-actin as the control group. Results : Curcumin has a biphasic effect on SC-NPC proliferation. Lower dosage (0.1, 0.5, $1{\mu}M$) of curcumin increased SC-NPC proliferation. However, higher dosage decreased SC-NPC proliferation. Also, curcumin stimulates proliferation of SC-NPCs via the MAP kinase signaling pathway, especially involving the p-ERK and p-38 protein. The p-ERK protein and p38 protein levels varied depending on curcumin dosage (0.5 and $1{\mu}M$, p<0.05). Conclusion : Curcumin can stimulate proliferation of SC-NPCs via ERKs and the p38 signaling pathway in low concentrations.

• Applied Biological Chemistry
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• 제51권2호
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• pp.129-135
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• 2008

Berberine은 전통적인 중의약재로 이용되어지는 isoquinoline alkaloid로 황련, 황백과 같은 식물에서 주로 추출되며, 약리효과로는 항암, 항염, 항균과 같은 다양한 효과를 나타내는 것으로 알려져 있다. 그러나 간암세포에서 berberine의 산화적 스트레스에 의한 세포사멸기전에 대해서는 아직 밝혀진 바 없다. 따라서 본 연구는 사람의 간암세포인 HepG2 세포에서 berberien의 세포사멸기전에 reactive oxygen species(ROS)와 MAP kinase의 연관성을 조사하였다. Berberine은 HepG2 세포에서 처리 시간과 농도에 의존적으로 세포독성효과를 보였으며, $LD_{50}$은 berberine(50 ${\mu}M$) 처리 후 48시간에서 관찰 되었고, 세포고사의 특징인 핵의 응축 및 분절, DNA의 분절이 확인되었다. 또한 berberine에 의해 caspase-3, p53, p38 그리고 Bax의 발현이 현저하게 증가된 반면, anti-apoptotic 신호기전인 Bc1-2의 발현은 감소되었다. 이와 더불어 세포 내 nitric oxide(NO)와 ROS의 생성도 증가되었다. 본 연구 결과 HepG2 세포에서 berberine은 산화적 스트레스인 ROS와 NO의 생성을 유발하고 p38 MAP kinase와 p53의 인산화를 유도하였으며 미토콘드리아에서 Bcl-2의 감소와 bax의 증가, caspase-3의 활성을 경유하여 DNA의 손상을 통한 세포고사가 이루어지는 것을 확인 하였다.

• Molecules and Cells
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• 제28권6호
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• pp.583-588
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• 2009

The peroxiredoxin family of peroxidase has six mammalian members (Prx 1-6). Considering their frequent up-regulation in cancer cells, Prxs may contribute to cancer cells' survival in face of oxidative stress. Here, we show that Prx 6 promotes the invasiveness of lung cancer cells, accompanied by an increase in the activity of phosphoinositide 3-kinase (PI3K), the phosphorylation of p38 kinase and Akt, and the protein levels of uPA. Functional studies reveal that these components support Prx 6-induced invasion in the sequence p38 kinase/PI3K, Akt, and uPA. The findings provide a new understanding of the action of Prx 6 in cancer.