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Phospholipase Cγ의 생리적 기능과 질병과 연관된 돌연변이
장현준(Hyun-Jun Jang),최장현(Jang Hyun Choi),장종수(Jong-Soo Chang) 한국생명과학회 2020 생명과학회지 Vol.30 No.9
Phospholipase C gamma (PLCγ)는 phosphatidylinositol을 가수분해하여 신호전달 과정에 참여하는 PLC의 주요한 isotype으로 γ-specific array의 특징적인 구조를 바탕으로 receptor tyrosine kinases 및 non-receptor tyrosine kinase 신호를 주로 매개한다. PLCγ1과 PLCγ2의 두 isozyme이 존재하며 다양한 세포에서 발현하여 cell proliferation, migration 및 differentiation 등 여러 세포작용을 조절하고 있다. 최근의 연구들에서 PLCγ 돌연변이가 cancer와 immune disease 및 brain disorder 등에 연관된다는 것이 밝혀지고 있으며 genetic model을 통해 PLCγ의 생리적·병리적 기능이 제시되었다. 본 리뷰에서는 최신의 연구 결과들을 바탕으로 PLCγ의 구조와 활성 조절기전에 대해 기술하고 나아가 여러 질병의 발병과 진행에서 보고된 PLCγ의 돌연변이와 knockout 마우스를 활용한 연구 결과를 바탕으로 생리적·병리적 관점에서 PLCγ의 역할에 대해 고찰하였다. Phospholipase C gamma (PLCγ) has critical roles in receptor tyrosine kinase- and non-receptor tyrosine kinase-mediated cellular signaling relating to the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂] to produce inositol 1,4,5 trisphosphate (IP₃) and diacylglycerol (DAG), which promote protein kinase C (PKC) and Ca<SUP>2+</SUP> signaling to their downstream cellular targets. PLCγ has two isozymes called PLCγ1 and PLCγ2, which control cell growth and differentiation. In addition to catalytically active X- and Y-domains, both isotypes contain two Src homology 2 (SH2) domains and an SH3 domain for protein–protein interaction when the cells are activated by ligand stimulation. PLCγ also contains two pleckstrin homology (PH) domains for membrane-associated phosphoinositide binding and protein-protein interactions. While PLCγ1 is widely expressed and appears to regulate intracellular signaling in many tissues, PLCγ2 expression is restricted to cells of hematopoietic systems and seems to play a role in the regulation of immune response. A distinct mechanism for PLCγ activation is linked to an increase in phosphorylation of specific tyrosine residue, Y783. Recent studies have demonstrated that PLCγ mutations are closely related to cancer, immune disease, and brain disorders. Our review focused on the physiological roles of PLCγ by means of its structure and enzyme activity and the pathological functions of PLCγ via mutational analysis obtained from various human diseases and PLCγ knockout mice.
하고초, 감국, 갈근 약침이 비만쥐의 지질강하, 항산화 효과, TNF-α, IL-6 및 Leptin의 농도와 각종 장기의 해부조직학적 소견에 미치는 영향
장현준 ( Hyun Jun Jang ),이향숙 ( Hyang Sook Lee ),이준무 ( Joon Moo Lee ) 대한경락경혈학회 2007 Korean Journal of Acupuncture Vol.24 No.4
Objectives: We studied Effects of Hagocho(prunella vulgaris L.), Gamgook(chrysanthemum indicum L.) and Galgeun(pueraria Radix) aqua-acupuncture on the hyperlipidemic rat. methods: We investigated lowering lipid effect, oxidative capacity, concentration of TNF-α, IL-6, Leptin and histological consideration in hyperlipidemic rat. Forty male Sprague-Dawley rats weighing about 400g were divided into 5 groups of control, Ⅰ: Hagocho (prunella vulgaris L. )+Gamgook (chrysanthemum indicum L. ) and Gokji aqua-acupuncture, Ⅱ: Hagocho(prunella vulgaris L. )+Gamgook (chrysanthemum indicum L. ) and Joksamri aqua-acupuncture, Ⅲ: Hagocho(prunella vulgaris L. )+Galgeun(pueraria Radix)and Gokji aqua-acupuncture and Ⅳ: Hagocho (prunella vulgaris L. )+Galgeun(pueraria Radix) and Joksamri aqua-acupuncture. Results : Contents of plasma β-lipoprotein, contents of IL-6, TNF-α and leptin, Plasma triglyceride and glucose, plasma total cholesterol and LDL-cholesterol, liver total cholesterol, liver triglyceride, plasma and liver TBARS, free fatty acids showed a tendency to decrease in the aqua-acupuncture groups compared to those of control group. The activities of GOT and GPT showed no significantly different in all treatment groups. Values of super oxide dismutase, glutathione peroxidase and catalase activity showed a tendency to increase in the aqua-acupuncture groups. Histological consideration of heart, kidney and liver in the aqua-acupuncture groups showed slight vasodilation and fat accumulation compared to those of normal rat. Conclusions: These results indicated that prunella vulgaris L., chrysanthemum indicum L. and pueraria Radix aqua-acupuncture at gokji(LI11) and Joksamri(ST36) suppressed adipose tissue mass and lipid peroxidation and increased antioxidant system in hyperlipidemic rat.