• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
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• pp.96-96
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• 2003

Acyl-CoA synthetase 4는 생쥐에 있어서 거의 모든 조직에서 발현하며 아라키돈산에 특이적인 효소이다. 아라키돈산은 세포막의 인지질로부터 cPLA2에 의하여 유리되고 cyclooxygenase-1, -2에 의하여 eicosanoid로 변환된다. 이렇게 생산된 prostaglandin과 같은 eicosanoid는 배란, 수정, 임신에 있어서 중요한 기능을 수행하고 있다. 그러나 세포막으로부터 유리된 아라키돈산은 acyl-CoA synthetase 4에 의하여 다시 세포막으로 재에스테르화되어 eicosaniod의 생산을 조절하는 것으로 생각되어지고 있다. 또한 acyl-CoA synthetase 4 유전자 한쪽이 knock-out된 heterozygote mouse에서는 사산, 유산과 난소에 있어서 황체 수의 증가 등을 보고하고 있다. 그러므로 본 연구에서는 정상 생쥐 (C57BL/6) 임신 기간 중 acyl-CoA synthetase 4 유전자의 발현을 확인하기 위하여 자궁, 난소, 태아에서 RT-PCR을 수행하였다. 또한 cPLA2, cyclooxygenase-1, cyclooxygenase-2 유전자의 발현 양상을 분석하여 eicosanoid 생산에 관여하는 유전자 상호간의 발현 을 확인하였다. acyl-CoA synthetase 4는 임신 0 day에서부터 19.5 day까지 자궁과 난소에서 모두 발현하고 있었다. 또한 5.5 day에서부터 19.5 day까지의 태아에서도 그 발현이 확인되었다. 그리고 cPLA2와 cyclooxygenase-1은 acyl-CoA synthetase 4와 유사한 양상을 보였으나 cyclooxygenase-2는 임신기간 중의 자궁, 난소, 태아에서 전혀 발현하지 않았다. 그러므로 임신 중 생쥐 자궁, 난소, 태아에 있어서 eicosanoid 생산에는 cPLA2, cyclooxygenase-1, acyl-CoA synthetase 4 유전자가 관여하고 있는 것으로 생각된다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.21-22
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• 2001

Phospholipase A$_2$(PLA$_2$) comprise a family of enzymes that hydrolyze the acyl bond at the sn-2 position of phospholipids to generate free fatty acids including arachidonic acid and lysophospholipids. Distinct forms of PLA$_2$are involved in digestion, inflammation, and intercelluar-and intracellular signaling pathways. The released arachidonic acid, which is enriched at the sn-2 position, serves as the precursor for eicosanoids such as prostaglandins and leukotrienes. During oxygenation of arachidonic acid to hydroxy endoperoxide, reactive oxygen radicals are generated. On the other hand, lysophospholipids increase membrane fluidity and can be cytotoxic with its detergent-like action. Thus, the biochemical features of the products of PLA$_2$activity suggest that PLA$_2$may be implicated in many destructive cellular processes.

• Tuberculosis and Respiratory Diseases
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• 제68권2호
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• pp.55-61
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• 2010

Background: The underlying pathogenesis of fat embolism-induced acute lung injury (ALI) has not been elucidated. In the present study, the pathogenesis of fat embolism-induced ALI was probed in association with neutrophilic oxidative stress in oleic acid (OA)-induced ALI of S-D rats. Methods: OA was injected intravenously to provoke ALI in experimental rats. Five hours later, indices of ALI were measured to confirm the role of the neutrophilic respiratory burst. The effect of an inhibition of phospholipase A2 (PLA2) was also evaluated. Results: The accumulation of neutrophils in the lung due to OA caused increased neutrophilic oxidative stress in lung, which was ameliorated by mepacrine. What were the results from inhibition of PLA2. Conclusion: Excess neutrophilic oxidative stress contributes to OA-induced ALI, which is lessened by the inhibition of PLA2.

• Tuberculosis and Respiratory Diseases
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• 제60권4호
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• pp.437-450
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• 2006

연구배경 : 급성호흡곤란증후군의 병인론 중 산화성 스트레스는 페 모세혈관손상의 중요한 기전의 일부이다. 본 연구에서는 호중구에 의한 유리 산소기의 형성이 $PLA_2$의 활성화와 관계가 있음을 근거로 하여 calcium channel blocker인 diltiazem이 내독소에 의한 급성 폐손상에 미치는 영향을 알아보고자 하였다. 방법 : 체중 300 gm 내외의 수컷 Sprague-Dawley흰쥐에서 내독소를 이용하여 급성 폐손상을 유도하고 동시에 내독소 투여 60분전에 diltiazem (3 mg/kg)을 복강 내로 투여하였다. 급성 폐손상이 유도된 흰쥐에서 폐장의 $PLA_2$, 사람에게서 분리된 호중구에서의 $PLA_2$, 폐장의 MPO의 활성도, 폐세척액내의 호중구의 수, surfactant, 단백함량, 호중구에서의 유리 산소기의 생성 등을 측정하였다. 또한 광학 현미경 및 전자 현미경을 이용하여 형태학적인 변화를 관찰하였고, 동시에 전자현미경 세포화학법을 이용하여 폐장내의 유리 산소기의 생성도 검사 하였다. 결과 : 내독소 투여 후 5 시간 후에는 급성 폐손상이 유발되고 폐장 및 호중구의 $PLA_2$, MPO, 폐세척액내의 호중구수, 단백함량 및 surfactant의 함량이 높게 측정되었다. 형태학적으로는 내독소에 의한 급성 페손상이 확인되었고 전자현미경을 이용한 세포화학적 검사에서는 폐장 내 유리 산소기의 생성이 증가되었음을 확인하였다. Diltiazem은 이러한 모든 변화를 감소시키고, 호중구에서의 산소기의 생성도 감소시켜 내독소에 의한 급성 폐손상을 감소 시켰다. 결론 : Diltiazem을 이용한 $PLA_2$의 억제는 내독소에 의한 급성 페손상에서 호중구에 의한 산화성 스트레스를 경감함으로써 그 손상을 줄일 것으로 사료된다.

• 생약학회지
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• 제34권1호통권132호
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• pp.100-108
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• 2003

The regulation of plasma lipid level, particularly LDL cholesterol, represents the focus of current therapy for atherosclerosis. And $Lp-PLA_2$ is able to hydrolyse oxidized phosphatidylcholine within LDL into lyso-PC and oxidized fatty acids. $Lp-PLA_2$ is a potential biomarker of coronary heart disease and plays an important proinflammatory role in the progression of atherosclerosis. We investigated the inhibitory effects of methanol extracts of 224 natural plants on $Lp-PLA_2$ activity. Seven kinds of methanol extracts of tested plants showed above 50% inhibitory effect with the concentration of $100\;{\mu}g/ml$. The concentrated aqueous suspensions of each methanol extract were partitioned with n-hexane, $CHCl_3$, and EtOAc. Among them, EtOAc extracts of Astilbe chinensis var. davidii (root) and Pourthiaea villosa var. brunnea (leaf) significantly inhibited $Lp-PLA_2$ activity at the same concentration.

• Journal of Microbiology and Biotechnology
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• 제27권1호
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• pp.84-91
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• 2017

The concern over the use of melittin in honey bee venom due to its adverse reaction caused by allergens such as phospholipase A2 ($PLA_2$) and hyaluronidase (HYA) has been an obstacle towards its usage. We developed a novel single-step method for melittin purification and the removal of $PLA_2$ and HYA. This study explores the influence of pH, buffer compositions, salt concentration, and types of cation-exchange chromatography resins on the recovery of melittin and the removal of both HYA and $PLA_2$. Melittin was readily purified with a strong cation-exchange resin at pH 6.0 with sodium phosphate buffer. It resulted in a recovery yield of melittin up to 93% (5.87 mg from a total of 6.32 mg of initial melittin in crude bee venom), which is higher than any previously reported studies on melittin purification. $PLA_2$ (99%) and HYA (96%) were also successfully removed. Our study generates a single-step purification method for melittin with a high removal rate of $PLA_2$ and HYA, enabling melittin to be fully utilized for its therapeutic purposes.

• Bulletin of the Korean Chemical Society
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• 제35권1호
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• pp.250-252
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• 2014

Lipoprotein-associated phospholipase A2 (Lp-$PLA_2$) is a crucial enzyme in atherosclerosis as a potential drug target. The most remarkable Lp-$PLA_2$ inhibitory drug is Darapladib. We determined the binding pose of Darapladib to Lp-$PLA_2$ through docking study. Darapladib formed two hydrogen bonding interactions with the side chain of Tyr160 and Gln352 and several pi-pi interactions with aromatic and aliphatic hydrophobic residues of Lp-$PLA_2$. It is known that the dietylpropan-amine moiety of Darapladib has influence on the improvement of its oral bioavailability and we supposed this in our docking results.

• BMB Reports
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• 제41권8호
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• pp.560-567
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• 2008

The importance of lipids in cell signaling and tissue physiology is demonstrated by the many CNS pathologies involving deregulated lipid metabolism. One such critical metabolic event is the activation of phospholipase $A_2$ ($PLA_2$), which results in the hydrolysis of membrane phospholipids and the release of free fatty acids, including arachidonic acid, a precursor for essential cell-signaling eicosanoids. Reactive oxygen species (ROS, a product of arachidonic acid metabolism) react with cellular lipids to generate lipid peroxides, which are degraded to reactive aldehydes (oxidized phospholipid, 4-hydroxynonenal, and acrolein) that bind covalently to proteins, thereby altering their function and inducing cellular damage. Dissecting the contribution of $PLA_2$ to lipid peroxidation in CNS injury and disorders is a challenging proposition due to the multiple forms of $PLA_2$, the diverse sources of ROS, and the lack of specific $PLA_2$ inhibitors. In this review, we summarize the role of $PLA_2$ in CNS pathologies, including stroke, spinal cord injury, Alzheimer's, Parkinson's, Multiple sclerosis-Experimental autoimmune encephalomyelitis and Wallerian degeneration.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9417-9421
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• 2014

Background: Esophageal cancer is one of the most frequently occurring malignancies and the seventh leading cause of cancer-related deaths in the world. The esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer worldwide. Materials and Methods: Our goal in this study was to detect phospholipase A2 Group IIA (PLA2G2A) and cyclooxygenase-2 (COX-2) immuno-expression in ESCC in a high-risk population in China. Results: Positive expression of PLA2G2A protein was observed in 57.2% (166/290) of the cases, while COX-2 was found in 257 of 290 samples (88.6%), both PLA2G2A and COX-2 being expressed in 153 cases (52.8%), with a significant agreement (Kappa=0.091, p=0.031).Overexpression of PLA2G2A was significantly correlated with the depth of invasion (p=0.001). Co-expression of PLA2G2A and COX-2 not only significantly correlated with the depth of invasion (p=0.004) but also with TNM stage (p=0.04). Conclusions: Our results showed that in patients with ESCC, PLA2G2A overexpression and PLA2G2A co-expression with COX-2 is significantly correlated with advanced stage. The biological role and pathophysiologic regulation of PLA2G2A and COX-2 overexpression in ESCC deserve further investigation.

• 한국의류학회지
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• 제36권6호
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• pp.653-662
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• 2012

This study measured the effect of general pre-treatment on PLA fabrics to confirm the benefits of enzymatic processing on PLA fabrics in the textile industry as well as evaluated the hydrolytic activities of three lipases. The effects of lipase hydrolysis were analyzed through moisture regain, dyeing ability, tensile strength, and surface morphology. As a result, PLA fibers were easily damaged by a low concentration of sodium hydroxide and a low treatment temperature. The optimal treatment conditions of Lipase from Candida cylindracea were pH 8.0, $40^{\circ}C$, and 1,000 U. The optimal treatment conditions for Lipase from Candida rugosa were pH 7.2, $37^{\circ}C$, and 1,000 U. The optimal treatment conditions for Lipase from Porcine pancreas were pH 8.0, $37^{\circ}C$, and 2,000 U. The moisture regain and dyeing ability of PLA fabrics increased and the tensile strength of PLA fabrics decreased. The results of surface morphology revealed that there were some cracks due to hydrolysis on the surface of the fiber.