플라보노이드의 세포 신호전달 조절

이응룡,강근호,강용진,김우열,최혜연,김봉우,정효순,조쌍구 대한암예방학회 2007 Journal of cancer prevention Vol.12 No.3

Many studies revealed the neuroprotective, cardioprotective, and chemopreventive actions of dietary flavonoids. The plausible mechanistic interpretation of the various effects of flavonoids was concentrated on the anti-oxidant or free radical-scavenging properties of these phytochemicals, both in model systems and under in vivo conditions. While there has been a major focus on the anti-oxidant properties, there is an emerging view that flavonoids and their in vivo metabolites, do not act as conventional hydrogen-donating anti-oxidants, but they may exert regulatory functions in cells through actions at protein kinase or lipid kinase signaling pathways. Flavonoids and more recently their metabolites, have been reported to act at phosphoinositide 3-kinase (PI 3-kinase), Akt/protein kinase B (Akt/PKB), protein kinase C (PKC), mitogen activated protein kinase (MAP kinase), and various tyrosine kinases signaling cascades. Inhibitory or stimulatory actions at these pathways are likely to affect cellular function profoundly by altering the phosphorylation state of target molecules and by modulating gene expression. A clear understanding of the mechanisms of action of flavonoids, either as anti-oxidants or modulators of cellular signaling pathways, and the influence of their metabolism on these properties are key to the evaluation of these potent biomolecules as anti-cancer agents, cardio-protectants, and inhibitors of neurodegeneration. (Cancer Prev Res 12, 163-173, 2007)

플라보노이드의 세포 신호전달 조절

이응룡,강근호,강용진,김우열,최혜연,김봉우,정효순,조쌍구 충남대학교 형질전환복제돼지연구센터 2007 논문집 Vol. No.10

Many studies revealed the neuroprotective, cardioprotective, and chemopreventive actions of dietary flavonoids. The plausible mechanistic interpretation of the various effects of flavonoids was concentrated on the anti-oxidant or free radical-scavenging properties of these phytochernicals, both in model systems and under in vivo conditions. While there has been a major focus on the anti-oxidant properties. there is an emerging view that flavonoids and their in vivo metabolites. do not act as conventional hydrogen-donating anti-oxidants. but they may exert regulatory functions in cells through actions at protein kinase or lipid kinase signaling pathways. Flavonoids and more recently their metabolites. have been reported to act at phosphoinositide 3-kinase(PI 3-kinase). Akt/protein kinase B(Akt/PKB), protein kinase C (PKC), mitogen activated protein kinase(MAP kinase), and various tyrosine kinases signaling cascades. Inhibitory or stimulatory actions at these pathways are likely to affect cellular function profoundly by altering the phosphorylation state of target molecules and by modulating gene expression. A clear understanding of the mechanisms of action of flavonoids, either as anti-oxidants or modulators of cellular signaling pathways, and the influence of their metabolism on these properties are key to the evaluation of these potent biomolecules as anti-cancer agents, cardio-protectants, and inhibitors of neurodegeneration.

Modulation of Apoptosis in HaCaT keratinocytes via Differential Regulation of ERK Signaling Pathway by Flavonoids

Eung-Ryoung Lee(이응룡),Yong-Jin Kang(강용진),Jung-Hyun Kim(김정현),Ssang-Goo Cho(조쌍구) 한국생물공학회 2005 한국생물공학회 학술대회 Vol.2005 No.10

다양한 세포 기능 조절 기작으로서의 단백질 인산화

조쌍구,이응룡,김장용,안재연 대한암예방학회 2006 Journal of cancer prevention Vol.11 No.1

Lots of oncogenics factors including signaling molecules, reactive oxygen species, and receptor proteins are closely involved in protein phosphorylation. Protein phosphorylation is probably one of the most studied post-translational modification mechanism which is very important for regulating the activities of important regulatory proteins in cellular signaling pathways. Here, we shortly presented recent advances in the protein phosphorylation research. Despite of the many studies, more extensive and specific research tools are needed for more comprehensive understanding of the exact molecular targets and functions of the cellular kinases. Recently, several proteomics tools are developed to analyze the phosphoproteomes or kinomes and this highthroughput study on the protein phosphorylation would be very helpful for understanding the mechanisms of many cellular functions such as cell cycle, aging, cancer or neurodegeneration. For the proteomics study, more works are needed to be done with phosphopeptides, but phosphopeptides are difficult to analyse due to the poor ionising capacity under standard MALDI conditions. Several methods have been developed to deal with the low sensitivity and specificity of the phosphopeptide analysis. The optimisation of the approach is described for a standard model peptide and protein. (Cancer Prev Res 11, 1-8, 2006)

Recent Advances in Protein Phosphorylation Research and its Analytical Methods

안재연,이응룡,조쌍구 충남대학교 형질전환복제돼지연구센터 2007 논문집 Vol. No.10

인간 Keratinocyte HaCaT 세포에서 에토포사이드 또는 과산화수소에 의해 유도되는 아폽토시스에 미치는 플라보노이드들의 영향

조쌍구,안재연,강용진,최태원,이응룡 대한암예방학회 2006 Journal of cancer prevention Vol.11 No.1

Apoptosis is a fundamental cellular activity which allows for the maintenance of physiological balance and a protective mechanism against carcinogenesis. Recently, Flavonoids, a broadly distributed class of plant pigments, were known to regulate apoptosis and considerable scientific and therapeutic interest has focused on the structure and functions of these flavonoids in cancer chemotherapy. Despite of the many studies, the pro-oxidant/anti-oxidant properties of flavonoids remain debatable, and the detailed molecular mechanisms of their effects remain largely unknown. The objective, then, of the present work was to assess the apoptosis-modulating effects of several flavonoids in human keratinocyte HaCaT cells. In this study, we treated several flavonoids to human HaCaT keratinocytes and found that 3,4’-dihydroxy flavone and eriodictyol slightly increse cell viability, although other flavonoids including keamferol, quercetin, taxifolin, apigenin, naringenin and isohamnetin showed cell growth inhibition. 3,4’-dihydroxy flavone showed anti-apoptotic effect on etoposide or H2O2-induced cell death. Treatment of cells with 3,4’- dihydroxy flavone has decreased the nuclear fragmentation, PARP or pro-caspase 3 cleavage induced by etoposide or hydrogen peroxide in HaCaT keratinocytes. Taken together, our data strongly suggest that phytochemicals such as flavonoids and etoposide differentially regulate apoptosis in human HaCaT keratinocytes. (Cancer Prev Res 11, 58-64, 2006)

세포사멸 및 신경퇴행과 관련된 미토콘드리아 단백질들

성지현,정효순,조쌍구,정미영,이응룡 대한암예방학회 2006 Journal of cancer prevention Vol.11 No.3

Apoptosis is a programmed cell death which has a critical role in embryonic development and maintenance of homeostasis in various cells and tissues. The mitochondrian is the cellular power plant providing ATP for most processes requiring energy and also, has a decisive role in the regulation of apoptosis by controlling the release of some mitochondrial proteins such as cytochrome c, AIF, Smac/ Diablo, and Omi/HtrA2. Studies in mice gene-deleted for Omi/HtrA2 and AIF showed the involvement of these mitochondrial proteins in selective cell degeneration in the striatum and celebellar neurons. Mutation in the mitochodrial AAA protease gene, paraplegin, caused an autosomal form of hereditary spastic paraplegia and a distinctive apoptosis in corticospinal neuronal axon. Reactive oxygen species and a fault of respiratory chain in mitochondria contribute to various neurological disorders. However, the pathogenetic mechanisms of selective neurodegeneration is not completely known. The elucidation of biological functions of mitochondrial proteins may shed new light on the development of novel drug for the prevention and therapy for the human neurological diseases. (Cancer Prev Res 11, 256- 263, 2006)

과산화수소에 의해 유도되는 세포사멸을 저해하는 Bax Inhibitor-1

김수정,김정현,정효순,이응룡,조쌍구 대한암예방학회 2006 Journal of cancer prevention Vol.11 No.3

Bax Inhibitor-1 (BI-1) is an anti-apoptotic transmembrane protein that is related with Bcl-2 family proteins, but it does not belong to any known gene family of vertebrates. BI-1 seemed to be an ancient regulatory protein, as homologues of BI-1 exist in not only most eukaryotes but prokaryotes. Recent studies showed that overexpression of BI-1 were observed in several kinds of cancers and led to suppression of the apoptotic cell death. BI-1 was found to have anti-apoptotic and oncogenic effects, but the exact molecular mechanism for the effects was not completely understood. Here, in order to investigate the relationship between the anti-apoptotic functions of BI-1 and reactive oxygen species (ROS) production, we studied the effect of BI-1 overexpression on the hydrogen peroxide-induced apoptosis. Cell death was induced by hydrogen peroxide treatment in a dose-dependent manner and found to be suppressed by stable expression of human BI-1. From DAPI-staining nuclear fragmentation analysis, stable expression of human BI-1 was assessed to protect the cells against hydrogen peroxide-induced apoptosis. Moreover, BI-1 expression had effect on decreasing the intracellular ROS level induced by hydrogen peroxide-caused oxidative stress. These results indicate that BI-1 could suppress hydrogen peroxide-induced apoptosis by regulating intracellular ROS level. (Cancer Prev Res 11, 192-198, 2006)