• BMB Reports
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• 제49권4호
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• pp.220-225
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• 2016

Cancer cells have different characteristics due to the genetic differences where these unique features may strongly influence the effectiveness of therapeutic interventions. Here, we show that the spontaneous reactivation of extracellular signalregulated kinase (ERK), distinct from conventional ERK activation, represents a potent mechanism for cancer cell survival. We studied ERK1/2 activation in vitro in SW480 colorectal cancer cells. Although ERK signaling tends to be transiently activated, we observed the delayed reactivation of ERK1/2 in epidermal growth factor (EGF)-stimulated SW480 cells. This effect was observed even after EGF withdrawal. While phosphorylated ERK1/2 translocated into the nucleus following its primary activation, it remained in the cytoplasm during late-phase activation. The inhibition of primary ERK1/2 activation or protein trafficking, blocked reactivation and concurrently increased caspase 3 activity. Our results suggest that the biphasic activation of ERK1/2 plays a role in cancer cell survival; thus, regulation of ERK1/2 activation may improve the efficacy of cancer therapies that target ERK signaling.

• 한국식품과학회지
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• 제33권1호
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• pp.66-71
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• 2001

가열에 의한 품종별 고구마 조직의 변화에 대한 반응속도론적 상수를 biphasic model과 fractional conversion method를 사용하여 결정하였다. Biphasic model에 따라 고구마의 가열에 의한 조직의 변화는 2단계의 연속적인 1차 반응식으로 표시할 수 있었으며, 활성화에너지는 고구마의 품종에 따라 $71.0{\sim}75.1\;kJ/mol$ 및 $48.4{\sim}59.6\;kJ/mol$이었다. 또한 고구마의 가열에 의한 조직변화를 fractional conversion method를 사용하여 1개의 1차 반응식으로 표시할 수 있었는데, 이 때의 활성화에너지는 $67.5{\sim}75.3\;kJ/mol$로서 biphasic model에 의한 제 1단계의 반응에 대한 값과 유사한 값을 나타냈다. 이들 방법으로 결정된 반응속도론적 상수들 사이에는 kinetic compensation 효과가 있었으며, 두 방법 모두 고구마의 가열에 의한 조직변화에 대한 반응속도론적 상수들을 결정하는데 적용할 수 있음을 알 수 있었다.

• Bulletin of the Korean Chemical Society
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• 제32권12호
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• pp.4347-4351
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• 2011

The nucleophilic substitution reactions of ethylene phosphorochloridate (2) with X-pyridines are investigated kinetically in acetonitrile at $-20.0^{\circ}C$. The free energy correlations for substituent X variations in the nucleophiles exhibit biphasic concave upwards with a break point at X = 3-Ph. Unusual positive ${\rho}_X$ (= +2.49) and negative ${\beta}_X$ (= -0.41) values are obtained with the weakly basic pyridines, and rationalized by the isokinetic relationship with isokinetic temperature at $t_{ISOKINETIC}=6.6^{\circ}C$. The pyridinolysis rate of 2 with a cyclic five-membered ring is forty thousand times faster than its acyclic counterpart (3: diethyl chlorophosphate) because of great positive value of the entropy of activation of 2 (${\Delta}S^{\neq}$ = +49.2 eu) compared to negative value of 3 (${\Delta}S^{\neq}$ = -44.1 eu) over considerably unfavorable enthalpy of activation of 2 (${\Delta}H^{\neq}=28.4\;kcal\;mol^{-1}$) compared to 3 (${\Delta}H^{\neq}=6.3\;kcal\;mol^{-1}$). Great enthalpy and positive entropy of activation are ascribed to sterically congested transition state (TS) and solvent structure breaking in the TS. A concerted mechanism involving a change of nucleophilic attacking direction from a frontside attack with the strongly basic pyridines to a backside attack with the weakly basic pyridines is proposed.

• Bulletin of the Korean Chemical Society
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• 제33권1호
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• pp.270-274
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• 2012

The nucleophilic substitution reactions of 1,2-phenylene phosphorochloridate (1c) with X-pyridines are investigated kinetically in acetonitrile at $-25.0^{\circ}C$. The free energy correlations for substituent X variations in the nucleophiles exhibit biphasic concave upwards with a break point at X = 3-Ph. The pyridinolysis rate of 1c with a cyclic five-membered ring is $2.70{\times}10^5$ times faster than its acyclic counterpart (1a: phenyl ethyl chlorophosphate) because of great positive value of the entropy of activation of 1c (${\Delta}S^{\neq}$ = +26 eu) compared to negative value of 1a (${\Delta}S^{\neq}$= -24 eu) over considerably unfavorable enthalpy of activation of 1c (${\Delta}H^{\neq}=20.5kcal\;mol^{-1}$) compared to 1a (${\Delta}H^{\neq}=12.7kcal\;mol^{-1}$). Great enthalpy and positive entropy of activation are ascribed to sterically congested transition state (TS) and solvent structure breaking in the TS. A concerted mechanism involving a change of nucleophilic attacking direction from a frontside attack with the strongly basic pyridines to a backside attack with the weakly basic pyridines is proposed on the basis of greater selectivity parameters (${\rho}_X$ = -1.99 and ${\beta}_X$ = 0.41) with the strongly basic pyridines compared to those (${\rho}_X$ = -0.42 and ${\beta}_X$ = 0.07) with the weakly basic pyridines.

• 한국재료학회지
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• 제17권12호
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• pp.669-675
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• 2007

Hydroxyapatite (HAp) and biphasic calcium phosphate (BCP) nano powders were synthesized using the microwave-assisted synthesis process dependent on pH and microwave irradiation time. The average size of a powder was less than 100 nm in diameter. Through in-vitro cytotoxicity tests by an extract dilution method, the HAp and BCP nano powders have shown to be cytocompatible for L-929 fibroblast cells, osteoblastlike MG-63 cells and osteoclast-like Raw 264.7 cells. The activation of osteoblast was estimated by alkaline phosphatase (ALP) activity. When the HAp and BCP were treated to MG-63 cells, alkaline phosphatase activities increased on day 3, compared with those of the untreated cells. Also, the collagen fibers increased when the HAp and BCP powders suspension were treated to MG-63 cells, compared to those of the untreated cells. Quantitative alizarin red S mineralization assays showed a trend toward increasing mineralization in osteoblast cultured with powder suspension. In conclusion, hydroxyapatite and biphasic calcium phosphate appeared to be a bone graft substitute material with optimal biocompatibility and could be further applied to clinical use as an artificial bone graft substitute.

• Bulletin of the Korean Chemical Society
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• 제32권12호
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• pp.4185-4190
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• 2011

The nucleophilic substitution reactions of ethylene phosphorochloridate (1c) with substituted anilines ($XC_6H_4NH_2$) and deuterated anilines ($XC_6H_4ND_2$) are investigated kinetically in acetonitrile at $5.0^{\circ}C$. The anilinolysis rate of 1c involving a cyclic five-membered ring is four thousand times faster than its acyclic counterpart (1a: diethyl chlorophosphate) because of great positive value of the entropy of activation of 1c (${\Delta}S^{\neq}=+30\;cal\;mol^{-1}K^{-1}$ compared to negative value of 1a (${\Delta}S^{\neq}=-45\;cal\;mol^{-1}K^{-1}$) over considerably unfavorable enthalpy of activation of 1c (${\Delta}H^{\neq}=27.7\;kcal\;mol^{-1}$) compared to 1a (${\Delta}H^{\neq}=8.3\;kcal\;mol^{-1}$). Great enthalpy and positive entropy of activation are ascribed to sterically congested transition state (TS) and solvent structure breaking in the TS. The free energy correlations exhibit biphasic concave upwards for substituent X variations in the X-anilines with a break point at X = 3-Me. The deuterium kinetic isotope effects are secondary inverse ($k_H/k_D$ < 1) with the strongly basic anilines and primary normal ($k_H/k_D$ > 1) with the weakly basic anilines and rationalized by the TS variation from a dominant backside attack to a dominant frontside attack, respectively. A concerted $S_N2$ mechanism is proposed and the primary normal deuterium kinetic isotope effects are substantiated by a hydrogen bonded, four-center-type TS.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2004년도 춘계학술대회
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• pp.43-48
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• 2004

• 한국독성학회:학술대회논문집
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• 한국독성학회 2004년도 춘계학술대회
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• pp.43-48
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• 2004

• The Korean Journal of Physiology and Pharmacology
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• 제21권6호
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• pp.687-694
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• 2017

Plumbagin, a hydroxy 1,4-naphthoquinone compound from plant metabolites, exhibits anticancer, antibacterial, and antifungal activities via modulating various signaling molecules. However, its effects on vascular functions are rarely studied except in pulmonary and coronary arteries where NADPH oxidase (NOX) inhibition was suggested as a mechanism. Here we investigate the effects of plumbagin on the contractility of skeletal artery (deep femoral artery, DFA), mesenteric artery (MA) and renal artery (RA) in rats. Although plumbagin alone had no effect on the isometric tone of DFA, $1{\mu}M$ phenylephrine (PhE)-induced partial contraction was largely augmented by plumbagin (${\Delta}T_{Plum}$, 125% of 80 mM KCl-induced contraction at $1{\mu}M$). With relatively higher concentrations (>$5{\mu}M$), plumbagin induced a transient contraction followed by tonic relaxation of DFA. Similar biphasic augmentation of the PhE-induced contraction was observed in MA and RA. VAS2870 and GKT137831, specific NOX4 inhibitors, neither mimicked nor inhibited ${\Delta}T_{Plum}$ in DFA. Also, pretreatment with tiron or catalase did not affect ${\Delta}T_{Plum}$ of DFA. Under the inhibition of PhE-contraction with L-type $Ca^{2+}$ channel blocker (nifedipine, $1{\mu}M$), plumbagin still induced tonic contraction, suggesting $Ca^{2+}$-sensitization mechanism of smooth muscle. Although ${\Delta}T_{Plum}$ was consistently observed under pretreatment with Rho A-kinase inhibitor (Y27632, $1{\mu}M$), a PKC inhibitor (GF 109203X, $10{\mu}M$) largely suppressed ${\Delta}T_{Plum}$. Taken together, it is suggested that plumbagin facilitates the PKC activation in the presence of vasoactive agonists in skeletal arteries. The biphasic contractile effects on the systemic arteries should be considered in the pharmacological studies of plumbagin and 1,4-naphthoquinones.

• Bulletin of the Korean Chemical Society
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• 제34권11호
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• pp.3218-3222
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• 2013

The aminolyses, anilinolysis and pyridinolysis, of bis(2-oxo-3-oxazolidinyl) phosphinic chloride (1) have been kinetically investigated in acetonitrile at 55.0 and $35.0^{\circ}C$, respectively. For the reactions of 1 with substituted anilines and deuterated anilines, a concerted SN2 mechanism is proposed based on the selectivity parameters and activation parameters. The deuterium kinetic isotope effects ($k_H/k_D$) invariably increase from secondary inverse to primary normal as the aniline becomes more basic, rationalized by the transition state variation from a backside to a frontside attack. For the pyridinolysis of 1, the authors propose a stepwise mechanism with a rate-limiting step change from bond breaking for more basic pyridines to bond formation for less basic pyridines based on the selectivity parameters and activation parameters. Biphasic concave upward free energy relationship with X is ascribed to a change in the attacking direction of the nucleophile from a frontside attack with more basic pyridines to a backside attack with less basic pyridines.