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4-Hydroxynonenal Induces Endothelial Cell Apoptosis via ROS and Peroxynitrite Generation
Sang Woon Chung(정상운),Su Bog Yee(이수복),Ji Young Lee(이지영),Mohammad Akbar Hossain(호세인 모하메드 악바르),Dong Hwan Kim(김동환),Jeong-Hyun Yoon(윤정현),Hae Young Chung(장정윤),Nam Deuk Kim(김남득) 한국생명과학회 2011 생명과학회지 Vol.21 No.7
지질과산화로부터 생성된 aldehyde 중 4-hydroxynonenal (HNE)는 산화적 손상과 관련된 다량의 arachidonic acids, linoleic acids 등으로부터 생성될 수 있다. 그러므로 HNE는 산화적 스트레스와 관련된 세포사에서 중요한 매개인자로 작용을 할 수가 있을 것이다. 본 연구는 HNE가 세포사를 유발할 것이라 가정하고, 먼저 흰쥐 전립선 유래 내피세포인 YPEN-1 세포에서 세포독성을 측정하였다. 세포생장 저해능력은 HNE를 5~15 μM 농도로 처리하여 형태적 변화와 MTT assay를 통하여 결과를 관찰하였다. 그 결과 HNE가 이 세포에서 핵형의 변화와 세포사를 유발시키는 것을 각각의 실험을 통해 확인이 되었다. 또한 이 사실을 단백질의 변화를 통하여 확인을 할 수가 있었다. HNE를 24시간 처리한 세포에서 poly(ADP-ribose) polymerase 단백질 분절이 매개되었고 Bax의 발현량이 증가하였다. 또한 세포내의 활성 산소종들을 발생시켰다. 이에 생성된 활성 산소종과 peroxynitrite가 세포사와 관련이 있는가를 밝히기 위하여 이들의 포식자들인 N-acetylcysteine과 penicillamine을 본 연구에서 사용하였다. 이들 포식자들에 의해 HNE에 의해 유도되는 세포사가 억제가 되었기에 산화적 활성화가 HNE에 의해 유도된 세포사와 관련이 있음을 알 수 있었다. 이러한 결과들은 HNE가 내피세포에서 ROS와 peroxynitrite 생성을 통하여 세포사를 일으킨다는 사실을 뒷받침해 준다. The formation of reactive lipid aldehydes, 4-hydroxynonenal (HNE) is shown to be derived from fatty acid hydroperoxides through the oxidative process. Among its known effects in cytotoxicity, HNE has been implicated in apoptotic cell death. To delineate its putative role as a potential mediator, we investigated the mechanism by which HNE induces apoptosis of endothelial cells (ECs). The anti-proliferative effects of HNE were tested through MTT assay after exposure to various concentrations (5~15 μM) of HNE. We observed apoptotic bodies with propidium iodide staining, and measured the HNE induction of endothelial apoptosis by flow cytometry assay. We observed that cells exposed to HNE for 24 hr resulted in increased poly(ADP-ribose) polymerase cleavage and up-regulation of Bax. Data on the HNE action strongly indicated the involvement of reactive species, namely, intracellular ROS, nitrite, and peroxynitrite. To obtain evidence on the implication of ROS and peroxynitrite in HNE-induced apoptosis, a ROS scavenger, N-acetylcysteine (NAC), and a peroxynitrite scavenger, penicillamine, were tested. Results clearly indicate that the induction of apoptosis by HNE was effectively inhibited by NAC and penicillamine. Based on the present data, we conclude that the endothelial apoptosis induced by HNE involves both ROS generation and peroxynitrite activity. Our new data could lead to a redefinition of HNE action on apoptosis in ECs.
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Genomic Signature의 가시화방법에 의한 유전체의 분석
최정현,이석기,이수복,김영진,조환규,김규원 한국유전학회 2002 Genes & Genomics Vol.24 No.1
The concept of Genomic Signature (GS) is recently established to use as a method of analyzing genome of various species. This concept is pattern of unique base concentration, which is constructed whole genome of biological species. In order to visualize the GS, k-mer program which is based on the method of Chaos Game Representation (CGR) was used to analyze whole genome of various species. The data set used in this study was obtained from NCBI GenBank database and the analysis of GS using the data set compared similarity patterns of various signature lengths and was then visualized through k-mer graph. The k-mer graph allows depiction of frequencies of oligonucleotides in the form of image. As results, the k-mer graph of GS pattern was meaningful by being displayed in hexamer graph about various k lengths. Then we analyzed species-unique patterns of prokaryotic and eukaryotic genomes. We found the pattern of GS was maintained in 30 Kb length, which is less than 100 Kb length which is known as the length of GS in previous reports and the species-unique pattern among chromosomes in eukaryotes having several chromosomes. Therefore, we suggest that the analysis of GS by visualization of k-mer program may provide the clue to solve evolutionary relationship between species and component mechanisms of DNA maintenance.
ScienceON
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