• Proceedings of the Korea Society of Environmental Toocicology Conference
• /
• 2000.12a
• /
• pp.85-85
• /
• 2000

• Journal of Life Science
• /
• v.21 no.8
• /
• pp.1100-1108
• /
• 2011

The immunomodulating effects of moxifloxacin seem to be effective in downregulating inflammatory reactions. This presumed effect was tested in endotoxin (ETX)-induced acute lung injury (ALI) in rats. After moxifloxacin treatment (10 mg/kg) of ETX-given rats, lung myeloperoxidase (MPO) activity, bronchoalveolar-lavage (BAL) protein, and the number of neutrophils in the BAL cells were measured. Light and electron microscopic structures were also examined. Electron microscopic $CeCl_3$ histochemistry for the detection of hydrogen peroxide in the lungs and immunohistochemistry of cytosolic phospholipase A2 (cPLA2) in the lung tissues and BAL cells were performed. To examine the expression of TNF${\alpha}$ in the lungs, western blotting was carried out with the lung tissues. ETX had accumulated neutrophils in the lungs, which was followed by lung leak. Oxidative stress occurred, and increased expression of cPLA2 in the lung tissues and BAL cells was observed in the ETX-given rats. Simultaneously, the expression of TNF${\alpha}$ was enhanced by ETX. Moxifloxacin, however, decreased all these parameters, indicating that ALI may have been ameliorated. Moxifloxacin appears to ameliorate ETX-induced ALI partially through the suppression of cPLA2 in the lungs of rats.

• Journal of Ginseng Research
• /
• v.18 no.1
• /
• pp.44-48
• /
• 1994

In adrenaline-stimulated human platelets, panaxadiol (PD) and panaxatriol (PT) from Panax ginseng C.A. Meyer did not inhibit the $Ca^{2+}$-innux, but inhibited the formation of thromboxane $A_2$ and the platelet aggregations. It seems that PD and PT block a pathyway interconvefing arachidonic acids (20:4) to thromboxane $A_2$ (TX $A_2$), because the amount of $Ca^{2+}$ which phospholipase C or phospholipase $A_2$ requires to liberate 20 : 4 from membrane phospholipids was increased by PD and PT. These results mean that PH and PT have an antiplatelet effect by Inhibiting the formation of TX $A_2$.

• Journal of the Korean Chemical Society
• /
• v.48 no.2
• /
• pp.161-170
• /
• 2004

A series of ${\gamma}$-aminobutyric acid-derived, potent human cytosolic phospholipase A$_2$ inhibitors have been prepared from acyl cyanophosphoranes and amine derivatives in a convergent manner. The ${\alpha}$-keto amide functionalities in the inhibitors have been introduced as electrophilic fragments via direct coupling reactions between the labile ${\alpha},{\beta}$-diketo nitriles and ${\gamma}$-aminobutyric acid t-butyl ester derivatives at -78 $^{\circ}C$ in moderate to good yields.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2001.11a
• /
• pp.21-22
• /
• 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.

• Proceedings of the PSK Conference
• /
• 2003.04a
• /
• pp.198-199
• /
• 2003

Chronic inflammatory processes are associated with pathology of Alzheimer's disease(AD). The expression of both cyclooxygenase-2(COX-2) and phospholipase A2(PLA2) appears to be strongly activated during AD, indicating the importance of inflammatory gene pathways as a response to brain injury. Stimulation of heterotrimeric G protein-coupled receptors including muscarinic receptors activates cytosolic PLA2 and receptor-mediated activation of PLA2 generates free fatty acids (i.e., arachidonic acid). (omitted)

• Proceedings of the PSK Conference
• /
• 2003.04a
• /
• pp.111-113
• /
• 2003

Biosynthsis of prostaglandin E2 (PGE2), the most common prostanoid with potent and diverse bio-activities, is regulated by three sequential enzymatic steps composed of phospholipase A2, cyclooxygenase (COX), and prostaglandin E synthase (PGES). Recently, three distinct PGESs have been identified; two of them are membrane-bound enzymes, mPGES-1 and mPGES-2, and the third one is a cytosolic enzyme, cPGES. (omitted)

• The Korean Journal of Physiology and Pharmacology
• /
• v.5 no.4
• /
• pp.287-297
• /
• 2001

Contraction of smooth muscle is initiated by an increase in cytosolic $Ca^{2+}$ leading to activation of $Ca^{2+}$/ calmodulin-dependnet myosin light chain (MLC) kinase and phosphorylation of MLC. The types of contraction and signaling mechanisms mediating contraction differ depending on the region. The involvement of these different mechanisms varies depending on the source of $Ca^{2+}$ and the kinetic of $Ca^{2+}$ mobilization. $Ca^{2+}$ mobilizing agonists stimulate different phospholipases $(PLC-{\beta},\;PLD\;and\;PLA_2)$ to generate one or more $Ca^{2+}$ mobilizing messengers $(IP_3\;and\;AA),$ and diacylglycerol (DAG), an activator of protein kinase C (PKC). The relative contributions of $PLC-{\beta},\;PLA_2$ and PLD to generate second messengers vary greatly between cells and types of contraction. In smooth muscle cell derived form the circular muscle layer of the intestine, preferential hydrolysis of $PIP_2$ and generation of $IP_3$ and $IP_3-dependent\;Ca^{2+}$ release initiate the contraction. In smooth muscle cells derived from longitudinal muscle layer of the intestine, preferential hydrolysis of PC by PLA2, generation of AA and AA-mediated $Ca^{2+}$ influx, cADP ribose formation and $Ca^{2+}-induced\;Ca^{2+}$ release initiate the contraction. Sustained contraction, however, in both cell types is mediated by $Ca^{2+}-independent$ mechanism involving activation of $PKC-{\varepsilon}$ by DAG derived form PLD. A functional linkage between $G_{13},$ RhoA, ROCK, $PKC-{\varepsilon},$ CPI-17 and MLC phosphorylation in sustained contraction has been implicated. Contraction of normal esophageal circular muscle (ESO) in response to acetylcholine (ACh) is linked to $M_2$ muscarinic receptors activating at least three intracellular phospholipases, i.e. phosphatidylcholine-specific phospholipase C (PC-PLC), phospholipase D (PLD) and the high molecular weight (85 kDa) cytosolic phospholipase $A_2\;(cPLA_2)$ to induce phosphatidylcholine (PC) metabolism, production of diacylglycerol (DAG) and arachidonic acid (AA), resulting in activation of a protein kinase C (PKC)-dependent pathway. In contrast, lower esophageal sphincter (LES) contraction induced by maximally effective doses of ACh is mediated by muscarinic $M_3$ receptors, linked to pertussis toxin-insensitive GTP-binding proteins of the $G_{q/11}$ type. They activate phospholipase C, which hydrolyzes phosphatidylinositol bisphosphate $(PIP_2),$ producing inositol 1, 4, 5-trisphosphate $(IP_3)$ and DAG. $IP_3$ causes release of intracellular $Ca^{2+}$ and formation of a $Ca^{2+}$-calmodulin complex, resulting in activation of myosin light chain kinase and contraction through a calmodulin-dependent pathway.

• The Korean Journal of Physiology and Pharmacology
• /
• v.14 no.3
• /
• pp.163-167
• /
• 2010

This study investigated the effects of the methanol extracts of Morinda citrifolia containing numerous anthraquinone and iridoid on phospholipase $A_2$ ($PLA_2$) isozyme. $PLA_2$ activity was measured using various $PLA_2$ substrates, including 10-pyrene phosphatidylcholine, 1-palmitoyl-2-[$^{14}C$]arachidonyl phosphatidylcholine ([$^{14}C$]AA-PC), and [$^3H$]arachidonic acid (AA). The methanol extracts suppressed melittin-induced [$_3H$]AA release in a concentration-dependent manner in RAW 264.7 cells, and inhibited $cPLA_2/sPLA_2$-induced hydrolysis of [$^{14}C$]AA-PC in a concentration- and time-dependent manner. A Dixon plot showed that the inhibition by methanol extracts on $cPLA_2$ and $sPLA_2$ appeared to be competitive with inhibition constants ($K_i$) of $3.7{\mu}g/ml$ and $12.6{\mu}g/ml$, respectively. These data suggest that methanol extracts of Morinda citrifolia inhibits both $Ca^{2+}$-dependent $PLA_2$ such as, $cPLA_2$ and $sPLA_2$. Therefore, Morinda citrifolia may possess anti-inflammatory activity secondary to $Ca^{2+}$-dependent $PLA_2$ inhibition.

• Biomedical Science Letters
• /
• v.22 no.4
• /
• pp.127-139
• /
• 2016

A species of the fungal genus Cordyceps has been used as an ingredient of traditional Chinese medicine. In this study, we prepared cordycepin-enriched WIB-801CE, an ethanol extract from culture solution of Cordyceps militaris-hypha, and evaluated its antiplatelet effects on human platelet aggregation. WIB-801CE dose-dependently inhibited ADP-, collagen-, and thrombin-induced platelet aggregation. These antiplatelet effects by WIB-801CE were associated with the attenuation of thromboxane $A_2$ ($TXA_2$) production and serotonin release by ADP, collagen, and thrombin. The inhibition of $TXA_2$ production by WIB-801CE was due to the inhibition of cyclooxygenase-1, $TXA_2$ synthase, and cytosolic phospholipase $A_2$ activity. Therefore, these data suggest that WIB-801CE may be a beneficial component against protection from platelet aggregation-mediated thrombotic disease.