Activated ERbeta increases the expression of L-type Ca2+ channel and enhances the hypertrophic phenotype of neonatal rat hearts
碩士 === 國立成功大學 === 生理學研究所 === 101 === With the elevation of 17 β-estradiol (E2) from implantation to parturition during pregnancy, cardiac development from the embryonic to neonatal stages changes its growth pattern from hyperplasia to hypertrophy without increasing the ratio of heart to body weight....
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ndltd-TW-101NCKU51161222015-10-13T22:51:43Z http://ndltd.ncl.edu.tw/handle/39630339219013224822 Activated ERbeta increases the expression of L-type Ca2+ channel and enhances the hypertrophic phenotype of neonatal rat hearts 活化雌激素貝他增加心臟L型鈣離子通道及誘導新生鼠心臟生理性肥大外表型 Hsin-TzuWang 王忻慈 碩士 國立成功大學 生理學研究所 101 With the elevation of 17 β-estradiol (E2) from implantation to parturition during pregnancy, cardiac development from the embryonic to neonatal stages changes its growth pattern from hyperplasia to hypertrophy without increasing the ratio of heart to body weight. It is possible that E2 may induce cardiac hypertrophy in neonatal hearts. Now, two estrogen receptors are discovered. Deletion of ERβ increases the current of the L-type calcium channel, prolongs the duration of the cardiac cycle, and induces cardiac hypertrophy in adult mice but depletion of ERβ does not Our preliminary data showed higher levels of ERβ protein in pre-pubertal hearts than those in adult hearts. Therefore, the purpose of the study was to determine whether activation of ERβ by DPN increased the expression of L-type Ca2+ channels and enhanced the hypertrophic phenotype of neonatal hearts. Neonatal SD rats were injected with DPN (20 µg/kg/day) subcutaneously for 7 days. H9c2 derived from cardiac tissue-derived cardiomyoblasts were used to confirm our study in neonatal rats. A 7-day treatment with retinoic acid (RA), LIF, or isoproterenol which changed cell morphology and increased the expression of α-actinin and L-type calcium channel showed early sign of hypertrophic growth. Those were used as our positive controls in vitro. Our results indicated that both E2 and DPN did not affect heart rate, heart weight, and body weight. Compared with E2, DPN improved the inverse correlation between heart rate and the duration of an electrical cycle of the heart (QTc), enlarged the amplitude of the QRS complex in Lead I, and increased the relative abundance of calcium handling proteins and cytoskeletal proteins. Co-treatment with nifedipine increased the amplitude of the S wave in Lead I and heart rate. A 7-day culture with DPN in vitro, changed cell morphology as RA, LIF, or ISO without altering cell size and increased the protein expressions of ER β,L-type Ca2+ channel, α-actinin, and β-tubulin. Co-treatment with tamoxifen (ER αand ER β antagonist, 10-8M) or PHTPP (an ER βantagonist, 10-8M) lowered the positive effect of DPN on the expression of L-type Ca2+ channel protein expression. Knockdown of ER βinhibited L-type Ca2+ channel protein expression as well. Whole-cell patch clamp showed the increased current of L-type Ca2+ channel by DPN enhanced. These in vivo and in vitro results showed the increases of calcium-handling proteins, cytoskeletal proteins, calcium current, and the amplitude of the QRS complex in Lead I with the increased expression of ERβ suggesting the role of ER β in initiating early development of cardiac hypertrophy. Mei-Ling Tsai 蔡美玲 2013 學位論文 ; thesis 60 en_US |
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碩士 === 國立成功大學 === 生理學研究所 === 101 === With the elevation of 17 β-estradiol (E2) from implantation to parturition during pregnancy, cardiac development from the embryonic to neonatal stages changes its growth pattern from hyperplasia to hypertrophy without increasing the ratio of heart to body weight. It is possible that E2 may induce cardiac hypertrophy in neonatal hearts. Now, two estrogen receptors are discovered. Deletion of ERβ increases the current of the L-type calcium channel, prolongs the duration of the cardiac cycle, and induces cardiac hypertrophy in adult mice but depletion of ERβ does not Our preliminary data showed higher levels of ERβ protein in pre-pubertal hearts than those in adult hearts. Therefore, the purpose of the study was to determine whether activation of ERβ by DPN increased the expression of L-type Ca2+ channels and enhanced the hypertrophic phenotype of neonatal hearts. Neonatal SD rats were injected with DPN (20 µg/kg/day) subcutaneously for 7 days. H9c2 derived from cardiac tissue-derived cardiomyoblasts were used to confirm our study in neonatal rats. A 7-day treatment with retinoic acid (RA), LIF, or isoproterenol which changed cell morphology and increased the expression of α-actinin and L-type calcium channel showed early sign of hypertrophic growth. Those were used as our positive controls in vitro. Our results indicated that both E2 and DPN did not affect heart rate, heart weight, and body weight. Compared with E2, DPN improved the inverse correlation between heart rate and the duration of an electrical cycle of the heart (QTc), enlarged the amplitude of the QRS complex in Lead I, and increased the relative abundance of calcium handling proteins and cytoskeletal proteins. Co-treatment with nifedipine increased the amplitude of the S wave in Lead I and heart rate. A 7-day culture with DPN in vitro, changed cell morphology as RA, LIF, or ISO without altering cell size and increased the protein expressions of ER β,L-type Ca2+ channel, α-actinin, and β-tubulin. Co-treatment with tamoxifen (ER αand ER β antagonist, 10-8M) or PHTPP (an ER βantagonist, 10-8M) lowered the positive effect of DPN on the expression of L-type Ca2+ channel protein expression. Knockdown of ER βinhibited L-type Ca2+ channel protein expression as well. Whole-cell patch clamp showed the increased current of L-type Ca2+ channel by DPN enhanced. These in vivo and in vitro results showed the increases of calcium-handling proteins, cytoskeletal proteins, calcium current, and the amplitude of the QRS complex in Lead I with the increased expression of ERβ suggesting the role of ER β in initiating early development of cardiac hypertrophy.
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author2 |
Mei-Ling Tsai |
author_facet |
Mei-Ling Tsai Hsin-TzuWang 王忻慈 |
author |
Hsin-TzuWang 王忻慈 |
spellingShingle |
Hsin-TzuWang 王忻慈 Activated ERbeta increases the expression of L-type Ca2+ channel and enhances the hypertrophic phenotype of neonatal rat hearts |
author_sort |
Hsin-TzuWang |
title |
Activated ERbeta increases the expression of L-type Ca2+ channel and enhances the hypertrophic phenotype of neonatal rat hearts |
title_short |
Activated ERbeta increases the expression of L-type Ca2+ channel and enhances the hypertrophic phenotype of neonatal rat hearts |
title_full |
Activated ERbeta increases the expression of L-type Ca2+ channel and enhances the hypertrophic phenotype of neonatal rat hearts |
title_fullStr |
Activated ERbeta increases the expression of L-type Ca2+ channel and enhances the hypertrophic phenotype of neonatal rat hearts |
title_full_unstemmed |
Activated ERbeta increases the expression of L-type Ca2+ channel and enhances the hypertrophic phenotype of neonatal rat hearts |
title_sort |
activated erbeta increases the expression of l-type ca2+ channel and enhances the hypertrophic phenotype of neonatal rat hearts |
publishDate |
2013 |
url |
http://ndltd.ncl.edu.tw/handle/39630339219013224822 |
work_keys_str_mv |
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