• The Korean Journal of Physiology and Pharmacology
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• 제5권1호
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• pp.33-40
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• 2001

The aim of present study was to define the cellular mechanisms underlying changes in delayed rectifier $K^+\;(K_{DR})$ channel function in isoproterenol-induced hypertrophy. It has been proposed that $K_{DR}$ channels play a role in regulation of vascular tone by limiting membrane depolarization in arterial smooth muscle cells. The alterations of the properties of coronary $K_{DR}$ channels have not been studied as a possible mechanism for impaired coronary reserve in cardiac hypertrophy. The present study was carried out to compare the properties of coronary $K_{DR}$ channels in normal and hypertrophied hearts. These channels were measured from rabbit coronary smooth muscle cells using a patch clamp technique. The main findings of the study are as follows: (1) the $K_{DR}$ current density was decreased without changes of the channel kinetics in isoproterenol-induced hypertrophy; (2) the sensitivity of coronary $K_{DR}$ channels to 4-AP was increased in isoproterenol-induced hypertrophy. From the above results, we suggest for the first time that the alteration of $K_{DR}$ channels may limit vasodilating responses to several stimuli and may be involved in impaired coronary reserve in isoproterenol-induced hypertrophy.

• The Korean Journal of Physiology and Pharmacology
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• 제5권5호
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• pp.413-421
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• 2001

An impaired smooth muscle cell (SMC) relaxation of coronary artery by alteration of $K^+$ channels would be the most potential explanation for reduced coronary reserve in left ventricular hypertrophy (LVH), however, this possibility has not been investigated. We performed morphometrical analysis of the coronary artery under electron microscopy and measured $Ca^{2+}-activated\;K\;(K_{Ca})$ currents and delayed rectifier K $(K_{dr})$ currents by whole-cell and inside-out patch-clamp technique in single coronary arterial SMCs from rabbits subjected to isoprenaline-induced cardiac hypertrophy. Coronary arterial SMCs underwent significant changes in ultrastructure. The unitary current amplitude and the open-state probability of $K_{Ca}$ channel were significantly reduced in hypertrophy without open-time and closed-time kinetic. The concentration-response curve of $K_{Ca}$ channel to $Ca^{2+}$ is shifted to the right in hypertrophy. The reduction in the mean single channel current and increase in the open channel noise of $K_{Ca}$ channel by TEA were more sensitive in hypertrophy. $K_{dr}$ current density is significantly reduced in hypertrophy without activation and inactivation kinetics. The sensitivity of $K_{dr}$ current on 4-AP is significantly increased in hypertrophy. This is the first study to report evidence for alterations of $K_{Ca}$ channels and $K_{dr}$ channels in coronary SMCs with LVH. The findings may provide some insight into mechanism of the reduced coronary reserve in LVH.

• The Korean Journal of Physiology and Pharmacology
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• 제6권2호
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• pp.121-125
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• 2002

The pathophysiological implications of aldosterone and adrenomedullin in the cardiac ventricular hypertrophy were examined. Male Sprague-Dawley rats were treated with deoxycorticosterone acetate (DOCA)-salt and monocrotaline (MCT) to selectively elicit left and right ventricular (LV, RV) hypertrophy, respectively. The mRNA expression of aldosterone synthase and adrenomedullin in LV and RV was determined by reverse transcription-polymerase chain reaction. The expression of aldosterone synthase and adrenomedullin was increased in LV, while not altered significantly in RV of DOCA-salt-treated rats. On the contrary, the expression was not significantly altered in LV, but increased in RV of MCT-treated rats. The enhanced expression of aldosterone synthase may be causally related with the development of ventricular hypertrophy, and the increased expression of adrenomedullin may act as a counter-regulatory mechanism.

• BMB Reports
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• 제48권3호
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• pp.131-138
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• 2015

Cardiac hypertrophy is a form of global remodeling, although the initial step seems to be an adaptation to increased hemodynamic demands. The characteristics of cardiac hypertrophy include the functional reactivation of the arrested fetal gene program, where histone deacetylases (HDACs) are closely linked in the development of the process. To date, mammalian HDACs are divided into four classes: I, II, III, and IV. By structural similarities, class II HDACs are then subdivided into IIa and IIb. Among class I and II HDACs, HDAC2, 4, 5, and 9 have been reported to be involved in hypertrophic responses; HDAC4, 5, and 9 are negative regulators, whereas HDAC2 is a pro-hypertrophic mediator. The molecular function and regulation of class IIa HDACs depend largely on the phosphorylation-mediated cytosolic redistribution, whereas those of HDAC2 take place primarily in the nucleus. In response to stresses, posttranslational modification (PTM) processes, dynamic modifications after the translation of proteins, are involved in the regulation of the activities of those hypertrophy-related HDACs. In this article, we briefly review 1) the activation of HDAC2 in the development of cardiac hypertrophy and 2) the PTM of HDAC2 and its implications in the regulation of HDAC2 activity.

• The Korean Journal of Physiology and Pharmacology
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• 제5권2호
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• pp.147-156
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• 2001

It has been proposed that $Ca^{2+}-activated$ K $(K_{Ca})$ channels play an essential role in vascular tone. The alterations of the properties of coronary $K_{Ca}$ channels have not been studied as a possible mechanism for impaired coronary reserve in cardiac hypertrophy. The present studies were carried out to determine the properties of coronary $K_{Ca}$ channels in normal and hypertrophied hearts. These channels were measured from rabbit coronary smooth muscle cells using a patch clamp technique. The main findings of the present study are as follows: (1) the unitary current amplitudes and the slope conductance of coronary $K_{Ca}$ channels were decreased without changes of the channel kinetics in isoproterenol-induced cardiac hypertrophy; (2) the sensitivity of coronary $K_{Ca}$ channels to the changes of intracellular concentration of $Ca^{2+}$ was reduced in isoproterenol-induced cardiac hypertrophy. From above results, we suggest for the first time that the alteration of $K_{Ca}$ channels are involved in impaired coronary reserve in isoproterenol-induced cardiac hypertrophy.

• The Korean Journal of Physiology and Pharmacology
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• 제5권1호
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• pp.65-70
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• 2001

The present study was aimed to explore pathophysiological implications of nitric oxide in the development of left and right ventricular hypertrophy. To induce selective left and right ventricular hypertrophy, rats were made two-kidney, one clip (2K1C) hypertensive and treated with monocrotaline (MCT), respectively. Six weeks later, the hearts were taken and their ventricular tissue mRNA and protein expression of endothelial constitutive isoform of nitric oxide synthase (NOS) were determined by reverse transcription-polymerase chain reaction and Western blot analysis, respectively. In 2K1C hypertensive rats, the expression of NOS mRNA was increased in parallel with its proteins in the left ventricle, but not in the right ventricle. In MCT-treated rats, the expression of NOS mRNA and proteins were proportionally increased in the right ventricle, but not in the left ventricle. These results suggest that the expression of NOS is specifically increased in association with the ventricular hypertrophy, which may be a mechanism counteracting the hypertrophy.

• 한국음향학회지
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• 제28권8호
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• pp.790-795
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• 2009

본 연구는 구개편도와 아데노이드 비대가 있는 아동이 구호흡을 하게 되면 만성적인 성대 건조를 유발하게 되고, 이러한 조건이 음질을 저하시킬 수 있을 것이라는 가설을 검증하기 위하여, 만 5세-8세의 정상 아동 68명과 구개편도와 아데노이드 비대아동 50명을 대상으로 MDVP 음성분석을 시행하였다. 연구 결과 정상 아동에 비하여 구개편도와 아데노이드 비대 아동은 Jitt, RAP, PPQ, Shim, APQ 파라미터에서 모두 통계적으로 유의미하게 높은 수치를 나타내어 낮은 음질을 보이고 있음을 알 수 있었다. 따라서 언어치료사나 이비인후과 전문의 등은 구개편도와 아데노이드 비대 아동의 음성문제 가능성을 인식하고, 이들의 음성위생법 교육에 관심을 가져야 할 것으로 여겨진다.

• The Korean Journal of Physiology and Pharmacology
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• 제9권5호
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• pp.299-304
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• 2005

Cardiac hypertrophy contributes an increased risk to major cerebrovascular events. However, the molecular mechanisms underlying cerebrovascular dysfunction during cardiac hypertrophy have not yet been characterized. In the present study, we examined the molecular mechanism of isoproterenol (ISO)-evoked activation of Ras/Raf/MAPK pathways as well as PKA activity in cerebral artery of rabbits, and we also studied whether the activations of these signaling pathways were altered in cerebral artery, during ISO-induced cardiac hypertrophy compared to heart itself. The results show that the mRNA level of c-fos (not c-jun and c-myc) in heart and these genes in cerebral artery were considerably increased during cardiac hypertrophy. These results that the PKA activity and activations of Ras/Raf/ERK cascade as well as c-fos expression in rabbit heart during cardiac hypertrophy were consistent with previous reports. Interestingly, however, we also showed a novel finding that the decreased PKA activity might have differential effects on Ras and Raf expression in cerebral artery during cardiac hypertrophy. In conclusion, there are differences in molecular mechanisms between heart and cerebral artery during cardiac hypertrophy when stimulated with β2 adrenoreceptor (AR), suggesting a possible mechanism underlying cerebrovascular dysfunction during cardiac hypertrophy.

• Clinical and Experimental Pediatrics
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• 제57권7호
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• pp.323-328
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• 2014

Purpose: Adenoid hypertrophy is a physical alteration that may affect speech, and a speech disorder can have other negative effects on a child's life. Airway obstruction leads to constricted oral breathing and causes postural alterations of several oro-facial structures, including the mouth, tongue, and hyoid bone. The postural modifications may affect several aspects of speech production. Methods: In this study, we compared articulation errors in 19 children with adenoid hypertrophy (subject group) to those of 33 children with functional articulation disorders independent of anatomical problems (control group). Results: The mean age of the subject group was significantly higher (P=0.016). Substitution was more frequent in the subject group (P=0.003; odds ratio [OR], 1.80; 95% confidence interval [CI], 1.23- 2.62), while omission was less frequent (P<0.001; OR, 0.43; 95% CI, 0.27-0.67). Articulation errors were significantly less frequent in the palatal affricative in the subject group (P=0.047; OR, 0.25; 95% CI, 0.07-0.92). The number of articulation errors in other consonants was not different between the two groups. Nasalization and aspiration were significantly more frequent in the subject group (P=0.007 and 0.014; OR, 14.77 and 0.014; 95% CI, [1.62-135.04] and NA, respectively). Otherwise, there were no differences between the two groups. Conclusion: We identified the characteristics of articulation errors in children with adenoid hypertrophy, but our data did not show the relationship between adenoid hypertrophy and oral motor function that has been observed in previous studies. The association between adenoid hypertrophy and oral motor function remains doubtful.

• Molecules and Cells
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• 제37권1호
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• pp.81-87
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• 2014

Chronic pressure-overload cardiac hypertrophy is associated with an increased risk of morbidity/mortality, largely due to maladaptive remodeling and dilatation that progresses to dilated cardiomyopathy. Alternative splicing is an important biological mechanism that generates proteomic complexity and diversity. The recent development of next-generation RNA sequencing has improved our understanding of the qualitative signatures associated with alternative splicing in various biological conditions. However, the role of alternative splicing in cardiac hypertrophy is yet unknown. The present study employed RNA-Seq and a bioinformatic approach to detect the RNA splicing regulatory elements involved in alternative splicing during pressure-overload cardiac hypertrophy. We found GC-rich exonic motifs that regulate intron retention in 5' UTRs and AT-rich exonic motifs that are involved in exclusion of the AT-rich elements that cause mRNA instability in 3' UTRs. We also identified motifs in the intronic regions involved in exon exclusion and inclusion, which predicted splicing factors that bind to these motifs. We found, through Western blotting, that the expression levels of three splicing factors, ESRP1, PTB and SF2/ASF, were significantly altered during cardiac hypertrophy. Collectively, the present results suggest that chronic pressure-overload hypertrophy is closely associated with distinct alternative splicing due to altered expression of splicing factors.