Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D₂ in the beating rat atrium

Zhang, Ying,Li, Xiang,Liu, Li-Ping,Hong, Lan,Liu, Xia,Zhang, Bo,Wu, Cheng-Zhe,Cui, Xun The Korean Society of Pharmacology 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.3

Prostaglandin $D_2$ ($PGD_2$) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of $PGD_2$ in regulation of ANP secretion of the atrium was reported, the mechanisms involved are not clearly identified. The aim of the present study was to investigate whether $PGD_2$ can regulate ANP secretion in the isolated perfused beating rat atrium, and its underlying mechanisms. $PGD_2$ (0.1 to $10{\mu}M$) significantly increased atrial ANP secretion concomitantly with positive inotropy in a dose-dependent manner. Effects of $PGD_2$ on atrial ANP secretion and mechanical dynamics were abolished by AH-6809 ($1.0{\mu}M$) and AL-8810 ($1.0{\mu}M$), $PGD_2$ and prostaglandin $F2{\alpha}$ ($PGF2{\alpha}$) receptor antagonists, respectively. Moreover, $PGD_2$ clearly upregulated atrial peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and the $PGD_2$ metabolite 15-deoxy-${\Delta}12$, 14-$PGJ_2$ (15d-$PGJ_2$, $0.1{\mu}M$) dramatically increased atrial ANP secretion. Increased ANP secretions induced by $PGD_2$ and 15d-$PGJ_2$ were completely blocked by the $PPAR{\gamma}$ antagonist GW9662 ($0.1{\mu}M$). PD98059 ($10.0{\mu}M$) and LY294002 ($1.0{\mu}M$), antagonists of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling, respectively, significantly attenuated the increase of atrial ANP secretion by $PGD_2$. These results indicated that $PGD_2$ stimulated atrial ANP secretion and promoted positive inotropy by activating $PPAR{\gamma}$ in beating rat atria. MAPK/ERK and PI3K/Akt signaling pathways were each partially involved in regulating $PGD_2$-induced atrial ANP secretion.

Autophagy and ubiquitin-mediated proteolysis may not be involved in the degradation of spermatozoon mitochondria in mouse and porcine early embryos

Jin, Yong-Xun,Zheng, Zhong,Yu, Xian-Feng,Zhang, Jia-Bao,Namgoong, Suk,Cui, Xiang-Shun,Hyun, Sang-Hwan,Kim, Nam-Hyung Cambridge University Press 2016 Zygote Vol.24 No.1

<B>Summary</B><P>The mitochondrial genome is maternally inherited in animals, despite the fact that paternal mitochondria enter oocytes during fertilization. Autophagy and ubiquitin-mediated degradation are responsible for the elimination of paternal mitochondria in <I>Caenorhabditis elegans</I>; however, the involvement of these two processes in the degradation of paternal mitochondria in mammals is not well understood. We investigated the localization patterns of light chain 3 (LC3) and ubiquitin in mouse and porcine embryos during preimplantation development. We found that LC3 and ubiquitin localized to the spermatozoon midpiece at 3 h post-fertilization, and that both proteins were colocalized with paternal mitochondria and removed upon fertilization during the 4-cell stage in mouse and the zygote stage in porcine embryos. Sporadic paternal mitochondria were present beyond the morula stage in the mouse, and paternal mitochondria were restricted to one blastomere of 4-cell embryos. An autophagy inhibitor, 3-methyladenine (3-MA), did not affect the distribution of paternal mitochondria compared with the positive control, while an autophagy inducer, rapamycin, accelerated the removal of paternal mitochondria compared with the control. After the intracytoplasmic injection of intact spermatozoon into mouse oocytes, LC3 and ubiquitin localized to the spermatozoon midpiece, but remnants of undegraded paternal mitochondria were retained until the blastocyst stage. Our results show that paternal mitochondria colocalize with autophagy receptors and ubiquitin and are removed after <I>in vitro</I> fertilization, but some remnants of sperm mitochondrial sheath may persist up to morula stage after intracytoplasmic spermatozoon injection (ICSI).</P>

cAMP induction by ouabain promotes endothelin-1 secretion via MAPK/ERK signaling in beating rabbit atria

Li-qun Peng,Ping Li,Qiu-li Zhang,Lan Hong,Li-ping Liu,Xun Cui,Bai-ri Cui 대한생리학회-대한약리학회 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.1

Adenosine 3 ,5 -cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the Na⁺-K⁺-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain (3.0 μmol/L) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabainincreased atrial dynamics was blocked by KB-R7943 (3.0 μmol/L), an inhibitor for reverse mode of Na⁺-Ca²⁺ exchangers (NCX), but did not by L-type Ca²⁺ channel blocker nifedipine (1.0 μmol/L) or protein kinase A (PKA) selective inhibitor H-89 (3.0 μmol/L). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline (100.0 μmol/L), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP (0.5 μmol/L) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 (30 μmol/L), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.

cAMP induction by ouabain promotes endothelin-1 secretion via MAPK/ERK signaling in beating rabbit atria

Peng, Li-qun,Li, Ping,Zhang, Qiu-li,Hong, Lan,Liu, Li-ping,Cui, Xun,Cui, Bai-ri The Korean Society of Pharmacology 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.1

Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the $Na^+-K^+$-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain ($3.0{\mu}mol/L$) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 ($3.0{\mu}mol/L$), an inhibitor for reverse mode of $Na^+-Ca^{2+}$ exchangers (NCX), but did not by L-type $Ca^{2+}$ channel blocker nifedipine ($1.0{\mu}mol/L$) or protein kinase A (PKA) selective inhibitor H-89 ($3.0{\mu}mol/L$). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline ($100.0{\mu}mol/L$), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP ($0.5{\mu}mol/L$) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 ($30{\mu}mol/L$), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.

Mixing of initially stratified miscible fluids in an eccentric stirred tank: Detached eddy simulation and volume of fluid study

Feng Ling Yang,Shenjie Zhou,Cui Xun Zhang,Gui Chao Wang 한국화학공학회 2013 Korean Journal of Chemical Engineering Vol.30 No.10

Mixing of two stratified miscible fluids in an eccentric stirred tank agitated by a four pitched-blade turbine was studied by using the detached eddy simulation (DES) model and volume of fluid (VOF) method. The fluids were operated in the transitional and mildly turbulent flow regimes. Interfaces between the two miscible fluids during the mixing processes were captured and mixing times were computed. Effects of the Richardson number and eccentricity on the mixing times were quantificationally analyzed. Results show that the spatial and temporal variations of volume fractions of the fluids can be well captured by the method presented in this study. Mixing time increases with the increase of Richardson number. Effect of eccentricity on mixing time depends on Richardson number and the eccentric agitation scheme is not advisable to use to blend the low-viscosity miscible fluids starting from a stratified state, especially for lower Richardson values.

Turbulent flow and mixing performance of a novel six-blade grid disc impeller

Feng Ling Yang,Shenjie Zhou,Cui Xun Zhang 한국화학공학회 2015 Korean Journal of Chemical Engineering Vol.32 No.5

A novel six-blade grid disc impeller (RT-G) was designed and the single-phase turbulent flow and mixing in a baffled stirred tank agitated by this impeller were numerically studied by detached eddy simulation (DES) model. For comparison, a standard Rushton impeller (RT) with the same dimension was also investigated. The numerical results were compared with the reported experimental data and good agreements were obtained. Comparisons of the mean velocity, turbulent kinetic energy, power consumption and mixing time of RT and RT-G were performed. Results show that, for the tank stirred with RT-G, the velocity components can be increased in comparison with RT when the same power is consumed. The increase of the turbulent kinetic energy is about 20-30%. Besides, the mixing time for the tank stirred with RT-G is about 11% shorter than that of RT stirred tank operated at the same condition.

The WNT/Ca2+ pathway promotes atrial natriuretic peptide secretion by activating protein kinase C/transforming growth factor-β activated kinase 1/activating transcription factor 2 signaling in isolated beating rat atria

Li Zhi-yu,Liu Ying,Han Zhuo-na,Li Xiang,Wang Yue-ying,Cui Xun,Zhang Ying 대한약리학회 2022 The Korean Journal of Physiology & Pharmacology Vol.26 No.6

WNT signaling plays an important role in cardiac development, but abnormal activity is often associated with cardiac hypertrophy, myocardial infarction, remodeling, and heart failure. The effect of WNT signaling on regulation of atrial natriuretic peptide (ANP) secretion is unclear. Therefore, the purpose of this study was to investigate the effect of Wnt agonist 1 (Wnta1) on ANP secretion and mechanical dynamics in beating rat atria. Wnta1 treatment significantly increased atrial ANP secretion and pulse pressure; these effects were blocked by U73122, an antagonist of phospholipase C. U73122 also abolished the effects of Wnta1-mediated upregulation of protein kinase C (PKC) β and γ expression, and the PKC antagonist Go 6983 eliminated Wnta1-induced secretion of ANP. In addition, Wnta1 upregulated levels of phospho-transforming growth factor-β activated kinase 1 (p-TAK1), TAK1 banding 1 (TAB1) and phospho-activating transcription factor 2 (p-ATF2); these effects were blocked by both U73122 and Go 6983. Wnta1-induced ATF2 was abrogated by inhibition of TAK1. Furthermore, Wnta1 upregulated the expression of T cell factor (TCF) 3, TCF4, and lymphoid enhancer factor 1 (LEF1), and these effects were blocked by U73122 and Go 6983. Tak1 inhibition abolished the Wnta1-induced expression of TCF3, TCF4, and LEF1 and Wnta1-mediated ANP secretion and changes in mechanical dynamics. These results suggest that Wnta1 increased the secretion of ANP and mechanical dynamics in beating rat atria by activation of PKC–TAK1–ATF2–TCF3/LEF1 and TCF4/LEF1 signaling mainly via the WNT/Ca2+ pathway. It is also suggested that WNT–ANP signaling is implicated in cardiac physiology and pathophysiology.