Mitochondrial aldehyde dehydrogenase and cardiac diseases

Chen, Che‐Hong; Sun, Lihan; Mochly‐Rosen, Daria

doi:10.1093/cvr/cvq192

Cited by 184 publications

(188 citation statements)

References 91 publications

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“…However, high oxidative stress, such as that occurring after I/R or in heart failure may trigger lipid peroxidation and accumulation of reactive aldehydes, namely 4-HNE and malondialdehyde (11,25). Aldehydes inactivate a number of macromolecules, including the proteasome, the electron transport chain in the mitochondria, as well as ALDH2 itself (12). Indeed, treatment with ALDH2 activator Alda-1 increased ALDH2 activity by two-fold and reduced infarct size by 60% in an in vivo model of myocardial infarction in rats (11).…”

Section: Mao-b Activity Through Ros and Aldehydes Contribute To Altermentioning

confidence: 99%

Monoamine Oxidase B Prompts Mitochondrial and Cardiac Dysfunction in Pressure Overloaded Hearts

Kaludercic

Carpi

Nagayama

et al. 2014

Antioxidants & Redox Signaling

144

139

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Aims: Monoamine oxidases (MAOs) are mitochondrial flavoenzymes responsible for neurotransmitter and biogenic amines catabolism. MAO-A contributes to heart failure progression via enhanced norepinephrine catabolism and oxidative stress. The potential pathogenetic role of the isoenzyme MAO-B in cardiac diseases is currently unknown. Moreover, it is has not been determined yet whether MAO activation can directly affect mitochondrial function. Results: In wild type mice, pressure overload induced by transverse aortic constriction (TAC) resulted in enhanced dopamine catabolism, left ventricular (LV) remodeling, and dysfunction. Conversely, mice lacking MAO-B (MAO-B -/ -) subjected to TAC maintained concentric hypertrophy accompanied by extracellular signal regulated kinase (ERK)1/2 activation, and preserved LV function, both at early (3 weeks) and late stages (9 weeks). Enhanced MAO activation triggered oxidative stress, and dropped mitochondrial membrane potential in the presence of ATP synthase inhibitor oligomycin both in neonatal and adult cardiomyocytes. The MAO-B inhibitor pargyline completely offset this change, suggesting that MAO activation induces a latent mitochondrial dysfunction, causing these organelles to hydrolyze ATP. Moreover, MAO-dependent aldehyde formation due to inhibition of aldehyde dehydrogenase 2 activity also contributed to alter mitochondrial bioenergetics. Innovation: Our study unravels a novel role for MAO-B in the pathogenesis of heart failure, showing that both MAO-driven reactive oxygen species production and impaired aldehyde metabolism affect mitochondrial function. Conclusion: Under conditions of chronic hemodynamic stress, enhanced MAO-B activity is a major determinant of cardiac structural and functional disarrangement. Both increased oxidative stress and the accumulation of aldehyde intermediates are likely liable for these adverse morphological and mechanical changes by directly targeting mitochondria. Antioxid. Redox Signal. 20, 267-280.

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Section: Mao-b Activity Through Ros and Aldehydes Contribute To Altermentioning

confidence: 99%

Monoamine Oxidase B Prompts Mitochondrial and Cardiac Dysfunction in Pressure Overloaded Hearts

Kaludercic

Carpi

Nagayama

et al. 2014

Antioxidants & Redox Signaling

144

139

View full text Add to dashboard Cite

show abstract

“…4-HNE is one of the most abundant aldehydes formed during oxidation of polyunsaturated fatty and oxidative stress, and it is capable of modifying key enzymes by forming protein adducts to inhibit protein function (12). A recent study demonstrated that mechanical dysfunction of cardiomyocytes induced by 4-HNE was ablated by ALDH2 (25).…”

Section: R E S E a R C H A R T I C L Ementioning

confidence: 99%

“…Increasing evidence has revealed the beneficial role of ALDH2 against tissue and cellular injuries originated from alcohol, acetaldehyde and toxic aldehyde-induced reactive oxygen species formation (9-11). 4-HNE is a highly cytotoxic aldehyde that gets accumulated in the heart in response to ischemia/reperfusion insult, which in turn inactivates ALDH2 by protein adducts formation (12). Pharmacological enhancement of ALDH2 activity can protect the heart against ischemic injury (8).…”

Section: Introductionmentioning

confidence: 99%

Aldehyde Dehydrogenase-2 Deficiency Aggravates Cardiac Dysfunction Elicited by Endoplasmic Reticulum Stress Induction

Liao

Sun

Isse

et al. 2012

Mol Med

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Mitochondrial aldehyde dehydrogenase-2 (ALDH2) has been characterized as an important mediator of endogenous cytoprotection in the heart. This study was designed to examine the role of ALDH2 knockout (KO) in the regulation of cardiac function after endoplasmic reticulum (ER) stress. Wild-type (WT) and ALDH2 KO mice were subjected to a tunicamycin challenge, and the echocardiographic property was examined. Protein levels of six items-78 kDa glucose-regulated protein (GRP78), phosphorylation of eukaryotic initiation factor 2 subunit α (p-eIF2α), CCAAT/enhancer-binding protein homologous protein (CHOP), phosphorylation of Akt, p47 phox nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and 4-hydroxynonenal-were determined by using Western blot analysis. Cytotoxicity and apoptosis were estimated using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay and caspase-3 activity, respectively. ALDH2 deficiency exacerbated cardiac contractile dysfunction and promoted ER stress after ER stress induction, manifested by the changes of ejection fraction and fractional shortening. In vitro study revealed that tunicamycin significantly upregulated the levels of GRP78, p-eIF2α, CHOP, p47 phox NADPH oxidase and 4-hydroxynonenal, which was exacerbated by ALDH2 knockdown and abolished by ALDH2 overexpression, respectively. Overexpression of ALDH2 abrogated tunicamycin-induced dephosphorylation Akt. Inhibition of phosphatidylinositol 3-kinase using LY294002 did not affect ALDH2-conferred protection against ER stress, although LY294002 reversed the antiapoptotic action of ALDH2 associated with p47 phox NADPH oxidase. These results suggest a pivotal role of ALDH2 in the regulation of ER stress and ER stress-induced apoptosis. The protective role of ALDH2 against ER stress-induced cell death was probably mediated by Akt via a p47 phox NADPH oxidase-dependent manner. These findings indicate the critical role of ALDH2 in the pathogenesis of ER stress in heart disease.

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“…), polyurethane, smog, cigarette smoke or motor vehicle exhaust. With their malodorous properties, some dietary and aromatic aldehydes are accepted as additives in food and cosmetics (e.g., citral, cinnamaldehyde, benzaldehyde, and retinal), though many others are cytotoxic (Chen, et al, 2010). Aldehydes could interact with thiol compounds of some proteins, leading to structural and functional alterations of these molecules (Weiner, et al, 2008).…”

Section: Aldehydesmentioning

confidence: 99%

“…Overconsumption of ethanol has been related to liver disease and several gastrointestinal and upper aerodigestive cancers. Numerous other cytotoxic and reactive aldehydes have been shown to be linked with other types of diseases (Hofseth & Wargovich, 2007, Perluigi, et al, 2009, Chen, et al, 2010.…”

Section: Aldehydesmentioning

confidence: 99%