• Proceedings of the PSK Conference
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• 2001.10a
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• pp.214.2-215
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• 2001

• Journal of Life Science
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• v.25 no.2
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• pp.231-236
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• 2015

Angiotensin II (AngII) is an essential hormone that affects vascular physiology. For example, stimulation of vascular smooth muscle cells (VSMCs) rapidly induces vasoconstriction and results in the up-regulation of blood pressure. Chronic stimulation of VSMCs with AngII also results in hypertrophy. In this study, we confirmed an involvement of phosphatidylinositol 3-kinase (PI3K)-dependent calcium mobilization in AngII-induced generation of reactive oxygen species (ROS). Stimulation of rat aortic smooth muscle cells (RASMCs) with AngII significantly induced the generation of ROS in a dose- and time-dependent manner. AngII-induced generation of ROS was completely abolished by pharmacological inhibition of PI3K (with LY294002), but inhibition of the ERK signaling pathway had no effect. AngII-induced calcium mobilization was completely blocked by inhibition of PI3K, whereas inhibition of the ERK signaling pathway by PD98059 was ineffective. Depletion of extracellular calcium or inhibition of the L-type calcium channel by nifedipine completely blocked AngII-induced calcium mobilization. Depletion of extracellular calcium by EGTA and incubation of RASMCs with calcium-free medium both significantly blocked AngII-induced ROS generation. Inhibition of the L-type calcium channel also significantly blocked AngII-induced ROS generation. These results suggest that AngII-induced ROS generation is regulated by calcium mobilization, which, in turn, is modulated by a PI3K/L-type calcium channel signaling pathway.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2002.07a
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• pp.234-234
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• 2002

• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.595-611
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• 2002

Akt/PKB protein kinase B, ALI acute lung injury, ARDS acute respiratory distress syndrome, CREB C-AMP response element binding protein, ERK extracelluar signal-related kinase, fMLP fMet-Leu-Phe, G-CSF granulocyte colony-stimulating factor, IL interleukin, ILK integrin-linked kinase, JNK Jun N-terminal kinase, LPS lipopolysaccharide, MAP mitogen-activated protein, MEK MAP/ERK kinase, MIP-2 macrophage inflammatory protein-2, MMP matrix metalloproteinase, MPO myeloperoxidase, NADPH nicotinamide adenine dinucleotide phosphate, NE neutrophil elastase, NF-kB nuclear factor-kappa B, NOS nitric oxide synthase, p38 MAPK p38 mitogen activated protein kinase, PAF platelet activating factor, PAKs P21-activated kinases, PMN polymorphonuclear leukocytes, PI3-K phosphatidylinositol 3-kinase, PyK proline-rich tyrosine kinase, ROS reactive oxygen species, TNF-${\alpha}$ tumor necrosis factor-a.

• Journal of Life Science
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• v.32 no.11
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• pp.882-889
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• 2022

Breast cancer anti-estrogen resistance 3 (BCAR3) has been identified as one of the genes that induces anti-estrogen resistance in breast cancer. We have previously reported that BCAR3 activates promoters of c-Jun, activator protein-1, and the serum response element. In this study, we investigated the functional role of BCAR3 in the activation of the estrogen response element (ERE) in normal human breast MCF-12A cells. Transient expression of BCAR3 induced ERE activation, which was further increased by 17β-estradiol treatment but was not blocked by the anti-estrogen tamoxifen. Next, we studied the signaling pathway of BCAR3 leading to ERE activation. BCAR3-mediated ERE activation was inhibited by LY294002 and AZD5363, inhibitors of the phosphatidylinositol (PI) 3-kinase pathway, but not by PD98059 and U0126, inhibitors of the mitogen-activated protein kinase pathway. ERE activation was induced by the catalytic subunit p110α. of PI3-kinase or the active mutant of Akt, and this activation was not further increased by additional BCAR3 transfection. Based on these results, we propose that BCAR3 plays an important role in ERE activation through the PI3-kinase/Akt pathway in human breast MCF-12A cells.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.140-140
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• 2001

We have shown that PI3-kinase played an essential role in the ARE-mediated rGSTA2 induction by oxidative stress following sulfur amino acid deprivation (SAAD) (Kang et al., Mol. Pharmacol., 2000). Microsomal epoxide hydrolase (mEH), which detoxifies a variety of epoxide intermediates produced from various xenobiotics, is inducible by oxidative stress.(omitted)

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.82-82
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• 2002

• Food Science and Biotechnology
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• v.17 no.5
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• pp.1079-1085
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• 2008

The chemopreventive activity of sulforaphane (SFN) occurs through its inhibition of carcinogen-activating enzymes and its induction of detoxification enzymes. However, the exact mechanisms by which SFN exerts its anti-carcinogenic effects are not fully understood. Therefore, the mechanisms underlying the cytoprotective effects of SFN were examined in MCF-7 breast cancer cells. Exposure of cells to SFN (10 ${\mu}M$) induced a transcriptional change in the AKR1C3 gene, which is one of aldo-keto reductases (AKRs) family that is associated with detoxification and antioxidant response. Further analysis revealed that SFN elicited a dose- and time-dependent increase in the expression of both the NRF2 and AKR1C3 proteins. Moreover, this up-regulation of AKR1C3 was inhibited by pretreatment with antioxidant, N-acetyl-L-cysteine (NAC), which suggests that the up-regulation of AKR1C3 expression induced by SFN involves reactive oxygen species (ROS) signaling. Furthermore, pretreatment of cells with LY294002, a pharmacologic inhibitor of phosphatidylinositol 3-kinase (PI3K), suppressed the SFN-augmented Nrf2 activation and AKR1C3 expression; however, inhibition of PKC or MEK1/2 signaling with $G\ddot{o}6976$ or PD98059, respectively, did not alter SFN-induced AKR1C3 expression. Collectively, these data suggest that SFN can modulate the expression of the AKR1C3 in MCF-7 cells by activation of PI3K via the generation of ROS.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.3
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• pp.213-221
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• 2020

Salvianolic acid B (SAB) is an active phytocomponent of a popular Chinese herb called Radix Salvia militiorrhiza with numerous biological properties. The anti-psoriasis activity of SAB was examined by evaluating various psoriasis inflammatory and keratin markers against imiquimod (IMQ)-induced psoriasis on BALB/c mice. Totally 50 healthy BALB/c mice were evenly divided into 5 groups including control, drug control (SAB; 40 mg/kg), IMQ-induced psoriasis (5%), IMQ exposure and treated with SAB (40 mg/kg), or standard methotrexate (MTX; 1 mg/kg). Mice supplemented with either SAB or MTX significantly lowered the values of psoriasis area severity index (PASI), erythema, scaling, skin thickness, inflammatory markers (interleukin [IL]-22/23/17A/1β/6) and lipid peroxidation product (malondialdehyde). Also, IMQ exposed BALB/c mice treated with SAB or MTX display lesser histopathological changes with enhanced antioxidant activities (catalase, superoxide dismutase). Moreover, the protein expression of keratin markers (K16 and K17) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling proteins (pAkt/Akt and pPI3K/PI3K) were significantly downregulated after administration with SAB and MTX as compared with IMQ induced mice. Taking together, SAB and MTX significantly ameliorate psoriatic changes by inhibiting psoriatic inflammatory and keratin markers through abolishing PI3K/Akt signaling pathway. However, further studies (clinical trials) are needed to confirm the anti-psoriatic property of SAB before recommending to psoriasis patients.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.103-103
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• 2001

인간유방상피세포에서 H-ras가 침윤성과 세포 이동성을 유도한다는 것을 이 전연구에서 밝혔다. Phosphatidylinositol 3-kinase(PI3K)는 세포 이동성에서 중요한 역할을 하는 것으로 보고되고 있다. 본 연구에서 인간유방상피세포인 MCF10A에서 H-ras에 의해 유도된 침윤성에 PI3K가 어떠한 영향을 미치는지 살펴보고자 하였다. PI3K의 활성은 PI3K의 downstream molecule인 Akt의 인산화를 Western blot으로 확인하였다. Akt는 MCF10A, H-ras, N-ras MCF10A 세포에서 같은 정도로 발현되는 반면, 인산화된 Akt는 MCF10A 세포에 비해 H-ras MCF10A 세포와 N-ras MCF10A 세포에서 현저히 높게 나타났다. 이상의 결과로서 H-ras, N-ras 둘 다 PI3K를 활성화시키며, 침윤성과 세포이동성이 없는 N-ras MCF10A 세포에서도 PI3K가 활성화되었으므로, PI3K의 활성은 세포침윤성과 이동성을 유도하는데에 있어서 충분하지는 않음을 말해준다. PI3K의 저해제인 LY294002와 wortmannin을 세포에 처리하였을 때 세포침윤성과 이동성이 유의성 있게 감소되었다. 이상의 결과는 MCF10A 세포의 침윤성과 이동설에 있어서 PI3K의 활성이 충분하지는 않지만 반드시 필요하다는 것을 알 수 있었다.