• Biomolecules & Therapeutics
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• 제18권4호
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• pp.351-362
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• 2010

Nitric oxide (NO), synthesized from L-arginine by three isoforms of NO synthase (NOS), is a gaseous signaling molecule with an astonishingly wide range of biological and pathophysiological activities, including vasorelaxation, angiogenesis, anti-inflammation, and anti-apoptosis in mammalian cells. Recent studies have shown that NO donors and inhaled NO convert to biologically active NO under biological conditions and act as a signaling molecule in pathophysiological conditions. This review will discuss the roles of NO and its potential therapeutic implication in various human diseases, such as tumor, vascular regeneration, hypertension, wound healing, and ischemia-reperfusion injury.

• 대한수의학회지
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• 제40권4호
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• pp.691-699
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• 2000

We investigated the effects of nitric oxide (NO) donors, S-nitroso-L-cysteine (Cys-NO) and 3-morpholinosydnonimine hydrochloride (SIN-1), on the contractile and electrical activity of the circular muscle of guinea pig gastric antrum by using intracellular microelectrode technique. The gastric antral circular muscle showed spontaneous phasic contraction and slow wave of membrane potential. Cys-NO ($0.001{\sim}10{\mu}M$) and SIN-1 ($0.001{\sim}100{\mu}M$) reduced not only the tonic and phasic contraction but also the amplitude of slow wave in a concentration dependent manner. NO donors were more potent to inhibit phasic contraction than to do slow wave. These inhibitory effects of NO donors were mimicked by the membrane permeable guanosine-3',5'-cyclic monophosphate (cGMP) analogue, 8-bromo-cyclic GMP (8-br-cGMP, $10{\sim}300{\mu}M$). The inhibitory effects of SIN-1 and Cys-NO were antagonized by the guanylate cyclase inhibitor, 1H[ [1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, $10{\mu}M$). These results suggest that the inhibitory effects of NO donors on the mechanical and electrical activity is mainly mediated by cGMP pathway.

• Journal of Korean Neurosurgical Society
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• 제38권5호
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• pp.366-374
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• 2005

Objective : Nitric oxide[NO] is implicated in a wide range of biological processes in tumors and is produced in glioma. To investigate the role of NO and its interaction with the tumoricidal effects of anticancer drugs, we study the antitumor activities of NO donors, with or without anticancer drugs, in human glioma cell lines. Methods : U87MG and U373MG cells were treated with the NO donors sodium nitroprusside[SNP] and S-nitroso-N-acetylpenicillamine[SNAP], alone or in combination with the anticancer drugs 1,3-bis[2-chloroethyl]-1-nitrosourea[BCNU] and cisplatin. Cell viability, cell proliferation, DNA fragmentation, nitrite level, and the expression of Bcl-2 and Bax were determined. Results : NO was markedly increased after treatment with SNP or SNAP; however, the addition of the anticancer drugs did not significantly affect NO production NO donors or anticancer drugs reduced glioma cell viability and, in combination, acted synergistically to further decrease cell viability in a dose- and time-dependent manner. Cell proliferation was inhibited and apoptosis were enhanced by combined treatment. Bax expression was increased by combined treatment, whereas Bcl-2 expression was reduced. The antitumor cytotoxicity of NO donors and anticancer drugs differed according to cell type. Conclusion : BCNU or cisplatin can inhibit cell viability and proliferation of glioma cells and can induce apoptosis. These effects are further enhanced by the addition of a NO donor which modulates the antitumor cytotoxicity of chemotherapy depending on cell type. Further biological, chemical, and toxicological studies of NO are required to clarify its mechanism of action in glioma.

• 생명과학회지
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• 제21권4호
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• pp.486-493
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• 2011

Nitric oxide (NO) donors는 heme oxygenase-1 (HO-1)의 강력한 유도제이다. 그러나 NO donors에 의한 HO-1의 발현이 NO donor에 의해 방출되는 NO에 의한 직접적인 영향인지는 불분명하다. 본 연구에서 흰쥐의 무릎으로부터 분리 배양한 관절연골세포에서 HO-1의 발현에 NO donors의 영향을 조사하였다. NO donors (SIN-1, SNAP 그리고 SNP)는 HO-1의 mRNA와 단백질의 합성을 크게 증가시켰다. 그리고 NO의 표적 분자인 guanylate cyclase와 protein kinase G의 관련성을 살펴본 결과, NO donors에 의한 Nrf2와 HO-1의 발현증가와는 무관한 것으로 보였다. 흥미롭게도, NO scavenger인 carboxy-PTIO와 SOD mimetic TEMPOL은 NO donors에 의한 HO-1의 발현을 억제하였다. 게다가, peroxynitrite scavenger인 MnTBAP에 의해서도 Nrf2와 HO-1의 발현이 완전히 억제되었다. Peroxynitrite는 NO와 superoxide의 반응에 의해 세포 내에서 자연적으로 형성되는 물질이므로 peroxynitrite가 관절연골세포에서 HO-1의 발현에 직접적인 영향을 주는지를 관찰하였다. 관절연골세포에 peroxynitrite를 처리한 결과, 시간과 농도 의존적으로 Nrf2와 HO-1의 발현을 크게 증가시켰다. 본 실험 자료 는 NO donors에 의한 HO-1의 발현증가는 방출되는 NO의 직접적인 영향이라기 보다는 NO와 superoxide의 반응으로 형성되는 peroxynitrite에 의해 유도된다는 것을 시사한다.

• 약학회지
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• 제45권1호
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• pp.116-124
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• 2001

Nitric oxide is a labile, gaseous, broad spectrum second messenger that used in various tissues and cells. If it is induced by endogenously and exogenously in the neuronal cells, it is able to mediate analgesia or hyperalgesia at the periphery and in the spinal level respectively. This dual role of nitric oxide in the sensory system is very intriguing but has not been fully understood yet. In this experiment, acetylcholine (300 $\mu$g/paw), sodium nitroprusside (600 $\mu$g/paw), and L-arginine (300 $\mu$g/paw) represented antinociceptive effect to noxious topical stimulus, but pronociceptive responses followed by spinally application (20$\mu$g/5$\mu$l, 10$\mu$g/3$\mu$l, 500$\mu$g/5$\mu$l respectively). Calcium ion is critical element which activates nitric oxide synthase, therefore verapamil (300 $\mu$g/paw) and NOS inhibitor (20 mg/kg, L-NAME or L-NOArg) are injected into right hind paw (i.pl.). When verapamil is combined with NOS inhibitors analgesic effects through NO-cGMP pathway are inhibited as compared with ACh alone. Diluted formalin (2.5%), when injected into rats'hind paw (0.05 ml), elicited a biphasic algesic responses and nitric oxide had an analgesic effect on both $A\delta$ and C sensory nerve fibers which manipulate the phases respective1y. Nitric oxides, which produced from constitutive nitric oxide synthase, activated cyclooxygenase-type I and then prostaglandins are produced from them. So, indomethacin and ibuprofen, inhibitors of COX$_1$enzyme, when pretreated intraperitoneally (100 mg/kg) could reduce the hyperalgesic state. From these results, it is possible to imagine that the intrathecally administered NO donors expressed hyperalgesia through both long-term potentiation mechanism and arachidonic acid-prostaglandin cascade.

• Archives of Pharmacal Research
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• 제26권11호
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• pp.937-942
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• 2003

Nitric oxide(NO) induces apoptosis in human osteoblasts. Treatment with exogenous NO donors, SNAP (S-Nitroso-N-acelylpenicillamine) and SNP (sodium nitroprusside), to MG-63 osteoblasts resulted in apoptotic morphological changes, as shown by a bright blue-fluorescent condensed nuclei and chromatin fragmentation by fluorescence microscope of Hoechst 33258-staining. The activities of caspase-9 and the subsequent caspase-3-like cysteine proteases were increased during NO-induced cell death. Pretreatment with Z-VAD-FMK (a pancaspase inhibitor) or Ac-DEVD-CHO (a specific caspase-3 inhibitor) abrogated the NO-induced cell death. The NO donor markedly activated JNK, a stress-activated protein kinase in the human osteoblasts. This study showed that the inhibition of the JNK pathway markedly reduced NO-induced cell death. But neither PD98059 (MEK inhibitor) nor SB203580 (p38 MAPK inhibitor) had any effect on NO-induced death. Taken together, these results suggest that JNK/SAPK may be related to NO-induced apoptosis in MG-63 human osteoblasts.

• The Korean Journal of Physiology and Pharmacology
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• 제16권3호
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• pp.211-217
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• 2012

Recent studies have demonstrated that nitric oxide (NO) activates transient receptor potential vanilloid subtype 1 (TRPV1) via S-nitrosylation of the channel protein. NO also modulates various cellular functions via activation of the soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway and the direct modification of proteins. Thus, in the present study, we investigated whether NO could indirectly modulate the activity of TRPV1 via a cGMP/PKG-dependent pathway in cultured rat dorsal root ganglion (DRG) neurons. NO donors, sodium nitroprusside (SNP) and S-nitro-N-acetylpenicillamine (SNAP), decreased capsaicin-evoked currents ($I_{cap}$). NO scavengers, hemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), prevented the inhibitory effect of SNP on $I_{cap}$. Membrane-permeable cGMP analogs, 8-bromoguanosine 3', 5'-cyclic monophosphate (8bromo-cGMP) and 8-(4chlorophenylthio)-guanosine 3',5'-cyclic monophosphate (8-pCPT-cGMP), and the guanylyl cyclase stimulator YC-1 mimicked the effect of SNP on $I_{cap}$. The PKG inhibitor KT5823 prevented the inhibition of $I_{cap}$ by SNP. These results suggest that NO can downregulate the function of TRPV1 through activation of the cGMP/PKG pathway in peripheral sensory neurons.

• 대한수의학회지
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• 제41권4호
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• pp.485-495
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• 2001

It was investigated whether $Ca^{2+}$ and $K^+$ channels were involved in the inhibitory action of nitric oxide (NO) on the contractile and slow wave activity of guinea pig gastric antral circular muscle. The gastric antral circular muscle showed spontaneous phasic contraction and slow wave. NO donors, 3-morpholinosydnonimine hydrochloride (SIN-1, $0.01{\sim}100{\mu}M$) and S-nitroso-L-cysteine (CysNO, $0.001{\sim}10{\mu}M$), reduced not only the amplitude of phasic contraction but also that of slow wave in a concentration-dependent manner. Both the perfusion of $Ca^{2+}$-free solution and the administration of $Ni^{2+}$, a nonselective $Ca^{2+}$ channel blocker, reduced the phasic contraction as well as the amplitude and frequency of the slow wave. The effects of these treatments were similar to those of NO donors. Nifedipine ($10{\mu}M$), a specific L-type $Ca^{2+}$ channel blocker, abolished the phasic contraction and remarkably reduced the plateau of slow wave but had no profound effect on the upstroke of slow wave. In the whole-cell patch clamp mode, CysNO shifted the steady-state activation curve for L-type $Ca^{2+}$ current to the right and the steady-state inactivation curve to the left. Pretreatment of various $K^+$ channel blockers such as tetraethylammonium (1 mM), 4-aminopyridine (0.5 mM), glibenclamide (10 mM), apamin ($0.1{\mu}M$), and iberiotoxin ($0.1{\mu}M$) did not affect the inhibitory action of SIN-1. These results suggest that NO donors suppress mechanical and electrical activity of guinea pig gastric antral circular muscle by inhibition of L-type $Ca^{2+}$ channel rather than by activation of $K^+$ channels.

• Toxicological Research
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• 제12권2호
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• pp.195-201
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• 1996

Endotoxic shock causes death in humans and animals via extreme hypoperfusion of peripheral organs. A massive production of nitric oxide (NO) both from the endothelical cells and smooth muscle cells has been proposed as a possible mechanism in this process. Since NO attenuated the contractility to vasoconstricting agents such as norepinephrine (NE) by directly acting on the smooth muscle cells, this mechanism was considered mainly as a postsynaptic mechanism. In this research it was investigated whether NO, thus released, also participates in the presynaptic events for the regulation of vascular tone in endotoxic shock. The role of NO was studied by adding NO donors or NO synthase inhibitor $N^\omega $methyl-L-arginine (NMA) in stimulated sympathetic nerves of the mesenteric vascular bed and the Langendorff heart of rats. Sodium nitroprusside (SNP), an NO donor, reduced the pressor responses of isolated mesenteric artery either to electrical stimulation or exogenously administered phenylephrine (PE). In this mesentery, although neither agent influenced NE release, in the presence of the adrenergic $\alpha_2$-receptor antagonist yohimbine, elecrical stimulation-evoked NE release was augumented by SNP. In the heart SNP facilitated the NE release induced by electrical stimulation, while NMA had no effect. From these results it is proposed that there exists a local reflex phenomenon in the junction between the sympathetic nerve terminals and the smooth muscle of resistance blood vessels; by which sympathetic responses are reduced by NO at the postjunctional level while NO facilitates NE release contributing to augumentation of sympathetic tone. All these facts suggest that NO produced during endotoxic shock has dual effects: whereas NO blunts the vasoconstrictive activity of NE at the postsynaptic level, NO presynaptically facilitates the release of NE from sympathetic nerve terminals.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2022년도 추계학술대회
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• pp.159-159
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• 2022

Nitric oxide (NO) is a versatile signaling molecule, which is not only involved in plant growth and development but also regulates biological processes in response to biotic and abiotic stresses. Exogenous application of NO regulates the endogenous level of nitric oxide in response to stress conditions and therefore, NO donors are frequently used for stress alleviation. However, NO has very short half-life along with high reactivity. Therefore, conventional NO donors are often disadvantageous due to the relative instability of NO. On the contrary, development of NO releasing nanoparticles is a potential technique for enhancing the availability of NO in plants. Therefore, our aim was to synthesize such potential NO releasing nanoparticles which may be useful for application in agriculture. We have prepared Chitosan encapsulated S-nitrosoglutathione nanoparticles (GSNONP) and tried it with different concentrations for basic research in Arabidopsis thaliana. Our results suggest that lower concentration of this nanoparticle is highly effective for better growth of plants whereas higher concentration produces toxicity that leads to plant death. We observed better growth of Arabidopsis thaliana at 1µM concentration of the GSNONP compared to free GSNO.