The effects of lysophosphatidic acid on Cx43 gap junction in rat primary astrocytes

碩士 === 國立陽明大學 === 解剖學及細胞生物學研究所 === 100 === Gap junctions are widely distributed in astrocytes, where they play an important role in regulating the homeostasis of the central nervous system. Changes in gap junction intercellular communication (GJIC) may cause abnormal development of the brain and tri...

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Main Authors: Yang, Jennifer Y., 楊韻萱
Other Authors: Jiahn-Chun Wu
Format: Others
Language:en_US
Published: 2012
Online Access:http://ndltd.ncl.edu.tw/handle/52984758890949606111
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spelling ndltd-TW-100YM0053910142015-10-13T21:22:40Z http://ndltd.ncl.edu.tw/handle/52984758890949606111 The effects of lysophosphatidic acid on Cx43 gap junction in rat primary astrocytes 水解磷脂酸對大鼠星狀神經膠細胞間隙接合之影響 Yang, Jennifer Y. 楊韻萱 碩士 國立陽明大學 解剖學及細胞生物學研究所 100 Gap junctions are widely distributed in astrocytes, where they play an important role in regulating the homeostasis of the central nervous system. Changes in gap junction intercellular communication (GJIC) may cause abnormal development of the brain and trigger neurodegenerative diseases. In this study, we investigated the effects of the lysophosphatidic acid (LPA) on connexin43 (Cx43) gap junctions in rat primary astrocytes. Following LPA treatment, Cx43 protein expression was reduced in a dose-dependent manner. Short-term treatment (< 1 h) of astrocytes with LPA induced a significantly inhibition of GJIC without any change in Cx43 protein levels. Furthermore, LPA induced a significant increase in phospho-Src and extracellular signal-related kinase (pERK) levels at 15 minutes and maximum at 30 minutes. The LPA-induced GJIC inhibition was abolished by co-treatment of astrocytes with Src inhibitor PP2 or ERK inhibitor PD98059. The LPA-induced ERK activation could be prevented by PP2 co-treatment. Prolonged LPA treatment further reduced Cx43 protein expression and down-regulated Cx43 mRNA levels. Moreover, LPA induced a reduction in Cx43 immunoreactivity at cell-cell junctions and significantly inhibited the GJIC function. ERK activation was sustained at 6 hours and the LPA-induced Cx43 protein down-regulation was prevented by PD98059 co-treatment. Pretreatment of PD98059 could restore the LPA-reduced Cx43 immunoreactivity at cell-cell junctions. Our results exhibit that short-term treatment of the LPA reduces the GJIC through Src-ERK signaling cascade, whereas long-term LPA treatment not only sustains the inhibition of the GJIC, but also decreases Cx43 protein levels via ERK activation and eventually causes gap junction disassembly. Jiahn-Chun Wu 吳建春 2012 學位論文 ; thesis 40 en_US
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description 碩士 === 國立陽明大學 === 解剖學及細胞生物學研究所 === 100 === Gap junctions are widely distributed in astrocytes, where they play an important role in regulating the homeostasis of the central nervous system. Changes in gap junction intercellular communication (GJIC) may cause abnormal development of the brain and trigger neurodegenerative diseases. In this study, we investigated the effects of the lysophosphatidic acid (LPA) on connexin43 (Cx43) gap junctions in rat primary astrocytes. Following LPA treatment, Cx43 protein expression was reduced in a dose-dependent manner. Short-term treatment (< 1 h) of astrocytes with LPA induced a significantly inhibition of GJIC without any change in Cx43 protein levels. Furthermore, LPA induced a significant increase in phospho-Src and extracellular signal-related kinase (pERK) levels at 15 minutes and maximum at 30 minutes. The LPA-induced GJIC inhibition was abolished by co-treatment of astrocytes with Src inhibitor PP2 or ERK inhibitor PD98059. The LPA-induced ERK activation could be prevented by PP2 co-treatment. Prolonged LPA treatment further reduced Cx43 protein expression and down-regulated Cx43 mRNA levels. Moreover, LPA induced a reduction in Cx43 immunoreactivity at cell-cell junctions and significantly inhibited the GJIC function. ERK activation was sustained at 6 hours and the LPA-induced Cx43 protein down-regulation was prevented by PD98059 co-treatment. Pretreatment of PD98059 could restore the LPA-reduced Cx43 immunoreactivity at cell-cell junctions. Our results exhibit that short-term treatment of the LPA reduces the GJIC through Src-ERK signaling cascade, whereas long-term LPA treatment not only sustains the inhibition of the GJIC, but also decreases Cx43 protein levels via ERK activation and eventually causes gap junction disassembly.
author2 Jiahn-Chun Wu
author_facet Jiahn-Chun Wu
Yang, Jennifer Y.
楊韻萱
author Yang, Jennifer Y.
楊韻萱
spellingShingle Yang, Jennifer Y.
楊韻萱
The effects of lysophosphatidic acid on Cx43 gap junction in rat primary astrocytes
author_sort Yang, Jennifer Y.
title The effects of lysophosphatidic acid on Cx43 gap junction in rat primary astrocytes
title_short The effects of lysophosphatidic acid on Cx43 gap junction in rat primary astrocytes
title_full The effects of lysophosphatidic acid on Cx43 gap junction in rat primary astrocytes
title_fullStr The effects of lysophosphatidic acid on Cx43 gap junction in rat primary astrocytes
title_full_unstemmed The effects of lysophosphatidic acid on Cx43 gap junction in rat primary astrocytes
title_sort effects of lysophosphatidic acid on cx43 gap junction in rat primary astrocytes
publishDate 2012
url http://ndltd.ncl.edu.tw/handle/52984758890949606111
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