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제113회 대한화학회 학술발표회, 총회 및 기기전시회 안내 Revealing copper-overloaded endoplasmic reticulum by using novel fluorescent organelle-selective Cu2+ ion probes

2014년 2월 10일 14시 35분 03초
ORGN.P-604 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
4월 16일 (수요일) 16:00~19:00
저자 및
이윤학, 윤병권, 선우경, 강철훈1,*, 김종승*
고려대학교 화학과, Korea
1경희대학교 동서의학대학원, Korea
Copper ions play essential roles in various biological systems and its homeostasis is tightly controlled in the mammalian cells. However, imbalances in copper homeostasis are responsible for defects in copper export systems and central nervous system in Wilson’s disease as a genetic disorder by mutated ATP7B gene. Copper toxicity may contribute to the generation of reactive oxygen species (ROS), which can lead to cellular damage, oxidative stress and DNA damage. Its cytotoxic effects may involve malfunction of various organelles although the excess of copper ions is mainly accumulated in lysosome in the hepatocytes. However, its effect on subcellular organelle functions or copper uptake pathways is poorly understood. Therefore, we present the synthesis and development of organelle-selective fluorescent Cu2+ sensors, 1 and 2, bearing naphthalimide and dipicolylamine (DPA) units. Confocal microscopic images indicated that probes 1 and 2 are mainly localized in ER and lysosome, respectively. Upon addition of the excess copper ions to the living cells, probe 1 showed strongly quenched fluorescence intensity. Furthermore, inhibition of copper export system by sodium metavanadate (NaVO3), aggravates fluorescence quenching of probe 1, suggesting that the ER is the primary site for copper reservoir in the overloading condition. Therefore, organelle selective probe 1 could be a valuable tool to understand the detailed role of copper ions. In addition this approach could be applied to diagnose pathogenesis related to the copper ion level changes.