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| 1 | ALDH2 contributes to melatonin-induced protection against APP/PS1 mutation-prompted cardiac anomalies through cGAS-STING-TBK1-mediated regulation of mitophagy显示文摘Ample clinical evidence suggests a high incidence of cardiovascular events in Alzheimer’s disease(AD),although neither precise etiology nor effective treatment is available.This study was designed to evaluate cardiac function in AD patients and APP/PS1 mutant mice,along with circulating levels of melatonin,mitochondrial aldehyde dehydrogenase(ALDH2)and autophagy.AD patients and APP/PS1 mice displayed cognitive and myocardial deficits,low levels of circulating melatonin,ALDH2 activity,and autophagy,ultrastructural,geometric(cardiac atrophy and interstitial fibrosis)and functional(reduced fractional shortening and cardiomyocyte contraction)anomalies,mitochondrial injury,cytosolic mtDNA buildup,apoptosis,and suppressed autophagy and mitophagy.APP/PS1 mutation downregulated cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)levels and TBK1 phosphorylation,while promoting Aβaccumulation.Treatment with melatonin overtly ameliorated unfavorable APP/PS1-induced changes in cardiac geometry and function,apoptosis,mitochondrial integrity,cytosolic mtDNA accumulation(using both immunocytochemistry and qPCR),mitophagy,and cGAS-STING-TBK1 signaling,although these benefits were absent in APP/PS1/ALDH2−/−mice.In vitro evidence indicated that melatonin attenuated APP/PS1-induced suppression of mitophagy and cardiomyocyte function,and the effect was negated by the nonselective melatonin receptor blocker luzindole,inhibitors or RNA interference of cGAS,STING,TBK1,and autophagy.Our data collectively established a correlation among cardiac dysfunction,low levels of melatonin,ALDH2 activity,and autophagy in AD patients,with compelling support in APP/PS1 mice,in which melatonin rescued myopathic changes by promoting cGAS-STING-TBK1 signaling and mitophagy via an ALDH2-dependent mechanism. | Shuyi Wang Lin Wang Xing Qin Subat Turdi Dongdong Sun Bruce Culver Russel JReiter Xiaoming Wang Hao Zhou Jun Ren | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 9 |
| 2 | Mitochondrial aldehyde dehydrogenase(ALDH2)rescues cardiac contractile dysfunction in an APP/PS1 murine model of Alzheimer’s disease via inhibition of ACSL4-dependent ferroptosis显示文摘Alzheimer’s disease(AD)is associated with high incidence of cardiovascular events but the mechanism remains elusive.Our previous study reveals a tight correlation between cardiac dysfunction and low mitochondrial aldehyde dehydrogenase(ALDH2)activity in elderly AD patients.In the present study we investigated the effect of ALDH2 overexpression on cardiac function in APP/PS1 mouse model of AD.Global ALDH2 transgenic mice were crossed with APP/PS1 mutant mice to generate the ALDH2-APP/PS1 mutant mice.Cognitive function,cardiac contractile,and morphological properties were assessed.We showed that APP/PS1 mice displayed significant cognitive deficit in Morris water maze test,myocardial ultrastructural,geometric(cardiac atrophy,interstitial fibrosis)and functional(reduced fractional shortening and cardiomyocyte contraction)anomalies along with oxidative stress,apoptosis,and inflammation in myocardium.ALDH2 transgene significantly attenuated or mitigated these anomalies.We also noted the markedly elevated levels of lipid peroxidation,the essential lipid peroxidation enzyme acyl-CoA synthetase long-chain family member 4(ACSL4),the transcriptional regulator for ACLS4 special protein 1(SP1)and ferroptosis,evidenced by elevated NCOA4,decreased GPx4,and SLC7A11 in myocardium of APP/PS1 mutant mice;these effects were nullified by ALDH2 transgene.In cardiomyocytes isolated from WT mice and in H9C2 myoblasts in vitro,application of Aβ(20μM)decreased cell survival,compromised cardiomyocyte contractile function,and induced lipid peroxidation;ALDH2 transgene or activator Alda-1 rescued Aβ-induced deteriorating effects.ALDH2-induced protection against Aβ-induced lipid peroxidation was mimicked by the SP1 inhibitor tolfenamic acid(TA)or the ACSL4 inhibitor triacsin C(TC),and mitigated by the lipid peroxidation inducer 5-hydroxyeicosatetraenoic acid(5-HETE)or the ferroptosis inducer erastin.These results demonstrate an essential role for ALDH2 in AD-induced cardiac anomalies through regulation of lipid peroxidation and ferroptosis. | Zhi-yun Zhu Yan-dong Liu Yan Gong Wei Jin Elena Topchiy Subat Turdi Yue-feng Gao Bruce Culver Shu-yi Wang Wei Ge Wen-liang Zha Jun Ren Zhao-hui Pei Xing Qin | 2022 | Acta Pharmacologica Sinica2022，43，1： | 6 |
| 3 | Electrophysiological effects of haloperidol on isolated rabbit Purkinje fibers and guinea pigs papillary muscles under normal and simulated ischemia显示文摘目的: haloperidol 的服药过量与主要室的心律不齐,心脏的传导块,和突然的死亡被联系。实验是在正常、模仿的局部缺血下面在心脏的 Purkinje 纤维和乳突的肌肉在行动潜力上学习 haloperidol 的效果的这的目的在兔子和畿尼 pigs.Methods 调节:用标准细胞内部的微电极技术,我们在行动潜力参数上检验了 haloperidol 的效果[行动潜力振幅( APA ),阶段 0 最大的向上的一击速度(V_(最大)),在90%极化( APD90 )的行动潜力振幅,并且有效倔强的时期( ERP )]在兔子心脏的 Purkinje 纤维和畿尼猪心脏的乳突的房间,两件织物在是在下面模仿是化学家 conditions.Results :在 ischemicconditions 下面, haloperidol 的不同集中压抑 APA 并且在兔子 Purkinje fibers.Haloperidol ( 3 亩 mol/L )以aconcentration依赖的方式延长了 APD90 显著地沮丧的 APA 和延长 APD90 ,并且从 1 亩 mol/L , haloperidol 显示出重要消沉onV_(最大); ERP 显著地没被影响。分别地,在畿尼猪,心脏的乳突的肌肉,在 APA 的重要减小的阀值, V_( 最大) , EPR,和 APD90 是 10,0.3,1,和 1 亩 mol/L forhaloperidol.Conclusion : 与心脏的传导性的纸巾相比,乳突的肌肉对更敏感是化学家条件。在局部缺血下面, haloperidol 以 aconcentration 依赖的方式延长了 ERP 和 APD90 并且猛抛在 ERP 和 APD90 的 ischemia.Theshortening 在乳突的肌肉行动潜力导致的 V_( 最大) 的减少可以被 haloperidol 禁止。 | Subat TURDI Parhat KERRAM | 2007 | Acta Pharmacologica Sinica2007，28，8： | 3 |
| 4 | Biphasic effects of haloperidol on sodium currents in guinea pig ventricular myocytes显示文摘目的:在豚鼠在钠水流(I_( Na ))上学习 haloperidol 的效果室的 myocytes.Method :整个房间的补丁夹钳技术被采用在单个室的 myocytes.Results 在I_( Na )上评估 haloperidol 的 theeffects : Haloperidol ( 0.1-3umol/L )以一种集中依赖者方式禁止了I_( Na )与I_( Na )上的 haloperidol ( 0.3 umol/L )的 0.253+-0.015 umol/L.Theinhibition 率的 IC50 是22.14%+-0.02%,并且 maximumconductance 显著地是 reduced.Haloperidol 减少的 | Subat TURDI Parhat KERRAM | 2007 | Acta Pharmacologica Sinica2007，28，6： | 3 |
| 5 | Cardiac-specific overexpression of insulin-like growth factor I (IGF-1) rescues lipopolysaccharide-induced cardiac dysfunction and activation of stress signaling in murine cardiomyocytes显示文摘 | Zhao P Turdi S Dong F | 2009 | Shock2009，32，： | 1 |
| 6 | Transgenic overexpression of aldehyde dehydrogenase-2 rescues chronic alcohol intake-induced myocardial hypertrophy and contractile dysfunction 显示文摘 | Doser TA Turdi S Thomas DP | 2009 | Circula- tion2009，119，14： | 1 |
| 7 | Catalase alleviates cardiomyocyte dysfunction in diabetes: role of Akt, Forkhead transcriptional factor and silent information regulator 2 显示文摘 | TURDI S LI Q LOPEZ FL | 2007 | Life Sci2007，81，11： | 1 |
| 8 | Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction : role of autophagy 显示文摘 | Turdi S Han X Huff AF | 2012 | Free Radic Biol Med2012，53，6： | 1 |
| 9 | AMP-activated protein kinase deficiency exacerbates aging-induced myocardial contractile dysfunction显示文摘 | Turdi S Fan XJ Li J | 2010 | Aging Cell2010，9，： | 1 |
| 10 | Cardiac-specific overexpression ofinsulin-like growth factor I(IGF-1)rescues lipopolysaccharide-induced cardiac dysfunction and activation of stress signaling inmurine cardiomyocytes显示文摘 | Zhao P Turdi S Dong F | 2009 | Shock2009，32，1： | 1 |
| 11 | Transgenic overexpression of aldehydedehydrogenase-2 rescues chronic alcohol intake-induced myocardial hypertrophy and contractile dysfunction 显示文摘 | Doser TA Turdi S Thomas DP | 2009 | Circulation2009，119，14： | 1 |
| 12 | Acute methamphetamine exposure inhibits cardiac contractile function显示文摘 | TURDI S SCHAMBER RM ROE ND | 2009 | Toxicol Lett2009，189，2： | 1 |
| 13 | Transgenic overexpression of aldehyde dehydrogenase-2 rescues chronic alcohol intake-induced myocardial hypertrophy and contractile dysfunction显示文摘 | Doser T A Turdi S Thomas D P | 2009 | Circulation2009，119，14： | 1 |
| 14 | Transgenic overexpression of alde-hyde dehydrogenase 2 rescues chronic alcohol intake induced myocardialhypertrophy and contractile dysfunction显示文摘 | Dosa TA Turdi S Thomas DP | 2009 | Circulation2009，119，14： | 1 |
| 15 | Tauroursodeoxyeholic acid mitigates high fat dietinduced cardiomyocyte contractile and intracellular Ca2+ anomalies显示文摘 | Turdi S Hu N Ren J | 2013 | PLoS One2013，8，63： | 1 |
| 16 | Transgenic overexpression of aldehyde dehydrogenase-2 rescues chronic alcohol intake-in- duced myocardial hypertrophy and contractile dysfunction显示文摘 | Doser TA Turdi S Thomas DP | 2009 | Cir- culation2009，119，14： | 1 |
| 17 | Cardiomyocyte contractile dysfunction in the APPswejPSldE9 mouse model of alzheimer's disease显示文摘 | Turdi S Guo R Huff AF | 2009 | PLoS One2009，4，6： | 1 |
| 18 | Transgenic overexpression of aldehyde dehydrogenase - 2 rescues chronic alcohol intake - induced myocardial hypertrophy and contractile dysfunction 显示文摘 | Doser TA Turdi S Thomas DP | 2009 | Circulation2009，119，14： | 1 |
| 19 | Transgenic overex-pression of aldehyde dehydrogenase -2 rescues chronicalcohol intake-induced myocardial hypertrophy and con-tractile dysfunction 显示文摘 | Doser TA Turdi S Thomas DPf | 2009 | Circulation2009，119，14： | 1 |
| 20 | Catalase alleviates cardiomyocyte dysfunction in diabetes:role of Akt,Forkhead transcriptional factor and silent information regulator 2显示文摘 | Turdi S Li Q Lopez FL | 2007 | Life Sci2007，81，11： | 1 |
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