• 생명과학회지
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• 제9권2호
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• pp.160-168
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• 1999

Butyrate는 탄소사슬이 짧은 지방산 중 하나로 소화되지 않은 식이성 섬유의 혐기적 발효결과 포유동물의 위장관내에 millimolar 농도로 유지되며 대장의 상피세포에서 흡수되어 energy원으로 사용된다. 70%정도 confluent하게 자란 사람의 대장암세포주인 HT29 cell에 5mM sodium butyrate를 시간별로 처리하고 세포의 생존율, 암세포의 분화정도의 biomarker로 알려진 alkaline phosphatase 및 PLC-rl의 발현정도를 측정하였으며 sphingolipid의 생합성 및 ceramidase 활성도 측정하였다. Sodium butyrate 처리는 성장중인 HT29 cell의 부착을 저해하여 처리 1일째부터 세포수가 감소하였고 형질막 효소인 alkaline phosphatase의 발현을 증가시켰으며 PLC-${\gamma}$의 발현을 감소시켰다. 또한, 복합 sphingolipid들의 생합성을 측정한 결과, 세포성장의 저해와 함께 sphingomyelin은 2일째부터 감소하였으며, galactosyl ceramide는 1일째부터 급속히 감소하였다. 그러나 ceramide의 경우, 1일째는 처리하기 전보다 680dpm/mg protein정도 증가하였으며 2일째에는 다시 급속히 감소하였다. 또한 butyrate처리에 의하여 HT29 cell의 acid ceramidase와 neutral ceramidase활성이 저해됨을 관찰하였는데 그 결과 ceramide함량이 초기에 증가된 것으로 생각된다. 본 실험결과들로부터 HT29 cell의 sodium butyrate처리는 세포분화 또는 세포성장저해를 가져오는데 이와 함께 초기의 ceramide함량 및 alkaline phosphatase활성의 증가와 galactosylceramide함량 및 LC-rl 발현의 감소현상이 동반됨을 알 수 있다.

• Biomolecules & Therapeutics
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• 제20권6호
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• pp.526-531
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• 2012

During our on-going studies to identify bioactive compounds in medicinal herbs, we found that saucerneol F (SF), a naturally occurring sesquilignan isolated from Saururus chinensis (S. chinensis), showed in vitro anti-inflammatory activity. In this study, we examined the effects of SF on the generation of 5-lipoxygenase (5-LO) dependent leukotriene $C_4$ ($LTC_4$), cyclooxygenase-2 (COX-2) dependent prostaglandin $D_2$ ($PGD_2$), and on phospholipase $C{\gamma}1$ ($PLC{\gamma}1$)-mediated degranulation in SCF-induced mouse bone marrow-derived mast cells (BMMCs). SF inhibited eicosanoid ($PGD_2$ and $LTC_4$) generation and degranulation dose-dependently. To identify the molecular mechanisms underlying the inhibition of eicosanoid generation and degranulation by SF, we examined the effects of SF on the phosphorylation of $PLC{\gamma}1$, intracellular $Ca^{2+}$ influx, the translocation of cytosolic phospholipase $A_2$ ($cPLA_2$) and 5-LO, and on the phosphorylation of MAP kinases (MAPKs). SF was found to reduce intracellular $Ca^{2+}$ influx by inhibiting $PLC{\gamma}1$ phosphorylation and suppressing the nuclear translocations of $cPLA_2$ and 5-LO via the phosphorylations of MAPKs, including extracellular signal-regulated protein kinase-1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Taken together, these results suggest that SF may be useful for regulating mast cell-mediated inflammatory responses by inhibiting degranulation and eicosanoid generation.

• Radiation Oncology Journal
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• 제15권2호
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• pp.97-104
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• 1997

목적 : 근치적 목적으로 통상적인 방사선 단독치료 또는 유도화학 방사선 병용요법을 받은 편도암 환자들을 대상으로 생존율과 예후인자를 후향적으로 분석하여 이들 치료방법의 역할을 평가하고자 하였다. 대상 및 방법 : 1985년 11월부터 1993년 12월까지 근치적 목적의 통상적 방사선 치료를 받은 총 34명의 편도암 환자 중 16명은 방사선 단독치료를, 다른 18명은 유도화학 방사선 병용요법으로 치료하였고 유도화학 약제는 cisplatin과 5-fluorouracil 또는 pepleomycin으로 1회에서 3회까지 시행하였다. 방사선 치료는 6MV-X선으로 하루 1.8Gy씩 주 5회 시행하여 원발병소에는 55.0-86.4Gy(중앙값; 66.6), 경부 임파절 병소에는 55.8-90Gy(중앙값; 69.7)까지 시행하였다. 결과 :추적기간은 4-118개월(중앙값; 13.5)이었고 남녀비는 31:3 이었고 연령분포는 33-79세 (중앙값; 56.5)였다. 전체 환자의 5년 생존율은 $32\%$였다.. 병기 I+II(n=8), II(n=13), III(n=13)기의 5년 생존율은 각각 $47\%,\;29\%,\;25\%$였다(p=0.33). 병기 72(n=13), 73(n=10), 74(n=7)의 5년 생존율은 각각 $38\%,\;27\%,\;0\%$였고, 71환자 4명 중 3명은 25, 45, 53개월 현재 재발 또는 원격 전이없이 생존중이며 전체 T병기에서의 생존율의 경향은 유의한 차이가 있었다(p=0.01). 경부 임파절의 전이군(n=20, $59\%$)과 비전이군(n=14)의 5년 생존율은 각각 $32\%,\;31\%$였다(p=0.85). 방사선 단독치료군(n=16)과 유도화학 병용요법군(n=18)의 중앙 생존기간은 각각 9.5개월, 24개월이었고 5년 생존율은 각각 $22\%,\;38\%$였으나 통계적인 유의한 차이는 없었다(p=0.24). 원발암의 주위 조직으로의 침습여부에 따라 침습군(n=21)과 비침습군(n=13)의 5년 생존율은 각각 $28\%,\;38\%$였다(p=0.62). 방사선 치료기간에 따라 60일 이하군(n=10)과 61일 이상군(n=24)의 5년 생존율은 $60\%,\;18\%$였다(p=0.027). 현재 생존하고 있는 11명의 환자들은 모두 구강 건조, 발치, 충치, 연하 장애 그리고 하악골 괴사 1례 등 만기 후유증을 호소하였다. 5년 생존율에 영향을 미치는 예후인자로서 단일변량 분석으로는 방사선 치료기간의 장단과 원발암의 병기였고, 다변량 분석에서는 방사선 치료기간만이 가장 유의한 인자였다. 전체 환자 중 2명은 진단 당시 동시적 이증 원발암으로서 각각 구개수암, 구강저암이 있었고 다른 3명은 추적기간 17, 33, 36개월째에 이차성 원발암으로서 각각 식도암, 설암, 폐암이 진단되었다. 결론 : 유도화학방사선 병용요법 또는 통상적인 방사선 단독치료는 일부 소수 초기 병변에서 그 치료적 효과를 볼 수 있었으나 대부분의 진행된 병기에서는 저조한 효과를 보였고 생존자 전원은 심각한 만기 후유중을 호소하여, 결국 국소제어율의 상승과 함께 더 작은 일회 조사량으로 만기 후유증을 최소화하려는 생물학적인 측면을 고려하여 가급적 치료기간을 줄일 수 있는 다분 할조사가 시행되어야 할 것이고 이에 대한 전향적인 연구가 필요하다고 생각된다.

• 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.107-108
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• 2003

The epidermal growth factor (EGF) is an important signaling ligand for the mitogenesis of many cells. The EGF receptors use signaling molecule multicomplexes and dynamic protein networks for the transmission and amplification of the signals as well as for the regulation of the cellular responses. EGF signaling has been reported to be enhanced in various tumors by the overexpressed EGF receptor and/or the mediators such as phospholipase C-$\gamma$1(PLC$\gamma$1). (omitted)

• Archives of Pharmacal Research
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• 제29권1호
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• pp.67-72
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• 2006

The abnormal proliferation of aortic vascular smooth muscle cells (VSMCs) plays a central role in the pathogenesis of atherosclerosis and restenosis after angioplasty and possibly also in the development of hypertension. The present study was designed to examine the inhibitory effects and the mechanism of luteolin 7-glucoside (L7G) on the platelet-derived growth factor (PDGF)-BB-induced proliferation of VSMCs. L7G significantly inhibited the PDGF-BB-induced proliferation and the DNA synthesis of the VSMCs in a concentration-dependent manner. Pre-incubation of the VSMCs with L7G significantly inhibited the PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2), Akt and the phospholipase C $(PLC)-{\gamma}1$ activation. However, L7G had almost no affect on the phosphorylation of $PDGF-{\beta}$ receptor tyrosine kinase, which was induced by PDGF-BB. These results suggest that L7G inhibits the PDGF-BB-induced proliferation of VSMCs via the blocking of $(PLC)-{\gamma}1$, Akt, and ERK1/2 phosphorylation.

• BMB Reports
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• 제41권6호
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• pp.415-434
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• 2008

Phosphoinositide-specific phospholipase C is an effector molecule in the signal transduction process. It generates two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. Currently, thirteen mammal PLC isozymes have been identified, and they are divided into six groups: PLC-$\beta$, -$\gamma$, -$\delta$, -$\varepsilon$, -$\zeta$ and -$\eta$. Sequence analysis studies demonstrated that each isozyme has more than one alternative splicing variant. PLC isozymes contain the X and Y domains that are responsible for catalytic activity. Several other domains including the PH domain, the C2 domain and EF hand motifs are involved in various biological functions of PLC isozymes as signaling proteins. The distribution of PLC isozymes is tissue and organ specific. Recent studies on isolated cells and knockout mice depleted of PLC isozymes have revealed their distinct phenotypes. Given the specificity in distribution and cellular localization, it is clear that each PLC isozyme bears a unique function in the modulation of physiological responses. In this review, we discuss the structural organization, enzymatic properties and molecular diversity of PLC splicing variants and study functional and physiological roles of each isozyme.

• 한국미생물·생명공학회지
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• 제25권6호
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• pp.592-597
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• 1997

During the screening of inhibitors against phospholipase C (PLC) and the formation of inositol phosphates (IP$_{t}$) at NIH3T3${\gamma}$1 cells from microbial secondary metabolites, we selected a fungal strain MT60109 which was capable of producing an inhibitor. By the taxonomic studies, this fungus was identified as Pseudallescheria sp. MT60109 and an inhibitor of PLC was purified by BuOH extraction and chromatographic techniques from the culture broth of Pseudallescheria sp. MT60109. The inhibitor was identified as thielavin B by the physico-chemical properties and spectroscopic analysis of UV, FAB-MS, $^{1}$H, $^{13}$C-NMR, $^{1}$H-$^{1}$H COSY and HMBC. Thielavin B showed potent inhibitory activity against PLC purified from bovine brain with an IC$_{50}$ of 20 $\mu$M. And it also inhibited the formation of inositol phosphates in platelet-derived growth factor (PDGF) -stimulated NIH3T3${\gamma}$1 cells with an IC$_{50}$ of 20 $\mu$M.

• Archives of Pharmacal Research
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• 제27권1호
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• pp.94-98
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• 2004

Effects of dopaminergic drugs on the degranulation of mast cells (RBL-2H3 cells) and the nitric oxide production from macrophage cells (RAW 264.7) were studied. Among the dopaminergic agonists and antagonists tested, bromocriptine, 7-OH-DPAT, haloperidol, and clozapine showed potent inhibitions of mast cell degranualtion ($IC_{50} value, 5 \mu$ M). However, these dopaminergic agents did not affect the tyrosine phosphorylations of the signaling components of the high affinity IgE receptor ($Fc\varepsilonRI$), such as Syk, $PLC\gamma1$, and $PLC\gamma2$.; This suggested that these signaling components were not involved in the inhibition of the mast cell degranulation by these compounds. On the other hand, dopamine, bromocriptine, 7-OH-DAPT, and haloperidol markedly inhibited the nitric oxide production from RAW 264.7 cells ($IC_{50}$ values, 10-20$\mu$M). Bromocriptine, a dopamine agonist that is routinely used for the treatment of Parkinsons disease, inhibited the expression of the inducible nitric oxide synthase at an early stage of the LPS-induced protein expression in a dose-dependent manner. The results suggested that these dopaminergic agents, when used for the treatment of dopamine receptors-related diseases, such as Schizophrenia or Parkinsons disease, might have additional beneficial effects.

• 대한약학회:학술대회논문집
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• 대한약학회 2004년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.147.1-147.1
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• 2004

• Molecules and Cells
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• 제28권1호
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• pp.13-17
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• 2009

Basic fibroblast growth factor (bFGF) plays an important role in angiogenesis. However, the underlying mechanisms are not clear. $Mg^{2+}$ is the most abundant intracellular divalent cation in the body and plays critical roles in many cell functions. We investigated the effect of bFGF on the intracellular $Mg^{2+}$ concentration ($[Mg^{2+}]_i$) in human umbilical vein endothelial cells (HUVECs). bFGF increased ($[Mg^{2+}]_i$) in a dose-dependent manner, independent of extracellular $Mg^{2+}$. This bFGF-induced $[Mg^{2+}]_i$ increase was blocked by tyrosine kinase inhibitors (tyrphostin A-23 and genistein), phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY294002) and a phospholipase $C{\gamma}$ ($PLC{\gamma}$) inhibitor (U73122). In contrast, mitogen-activated protein kinase inhibitors (SB202190 and PD98059) did not affect the bFGF-induced $[Mg^{2+}]_i$ increase. These results suggest that bFGF increases the $[Mg^{2+}]_i$ from the intracellular $Mg^{2+}$ stores through the tyrosine kinase/PI3K/$PLC{\gamma}$-dependent signaling pathways.