Impaired development of mitochondria plays a role in the central nervous system defects of fetal alcohol syndrome

Xu, Yuping; Liu, Peng; Li, Yong

doi:10.1002/bdra.20110

Cited by 37 publications

(28 citation statements)

References 65 publications

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“…Similar findings have been obtained in studies with mitochondria from the liver 31,32 and brain 33 , where the maximum blood ethanol concentration is presumed to be no more than 30 mM. Similarly, in the liver acutely perfused with ethanol, the ATP content was lowered with about 60 mM of ethanol but not with about 10 mM of ethanol 34 but was shown to decrease with 10 to 70 mM ethanol when evaluated with 31 P nuclear magnetic resonance 35,36 .…”

Section: Discussionsupporting

confidence: 82%

Ethanol Dose- and Time-dependently Increases α and β Subunits of Mitochondrial ATP Synthase of Cultured Neonatal Rat Cardiomyocytes

2015

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Mitochondria are target subcellular organelles of ethanol. In this study, the effects of ethanol on protein composition was examined with 2-dimensional electrophoresis of protein extracts from cultured neonatal rat cardiomyocytes exposed to 100 mM ethanol for 24 hours. A putative β subunit of mitochondrial ATP synthase was increased, which was confirmed by Western blot. The cellular protein abundances in the α and β subunits of ATP synthase increased in dose (0, 10, 50, and 100 mM)-and time (0.5 hour and 24 hours)-dependent manners. The DNA microarray analysis of total RNA extract demonstrated that gene expression of the corresponding messenger RNAs of these subunit proteins did not significantly alter due to 24-hour ethanol exposure. Therefore, protein expression of these nuclear-encoded mitochondrial proteins may be regulated at the translational, rather than the transcriptional, level. Alternatively, degradation of these subunit proteins might be decreased. Additionally, cellular ATP content of cardiomyocytes scarcely decreased following 24-hour exposure to any examined concentrations of ethanol.Previous studies, together with this study, have demonstrated that protein abundance of the α subunit or β subunit or both subunits of ATP synthase after ethanol exposure or dysfunctional conditions might differ according to tissue: significant increases in heart but decreases in liver and brain. Thus, it is suggested that the abundance of subunit proteins of mitochondrial ATP synthase in the ethanol-exposed heart, being different from that in the liver and brain, should increase dose-dependently through either translational upregulation or decreased degradation or both to maintain ATP production, as the heart requires much more energy than other tissues for continuing sustained contractions. (J Nippon Med Sch 2015; 82: 237 245)

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Section: Discussionsupporting

confidence: 82%

Ethanol Dose- and Time-dependently Increases α and β Subunits of Mitochondrial ATP Synthase of Cultured Neonatal Rat Cardiomyocytes

2015

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“…In addition, we reported recently that prenatal alcohol exposure downregulates several inner mitochondrial proteins such as ATP synthase, ubiquinol-cytochrome c, and ADP/ATP translocase in E13 fetal (Sari et al, 2010b). In accordance, studies have shown that intragastric prenatal alcohol exposure from E6-E15 induced a decrease in the activation of the cerebral mitochondrial respiratory chain complex I and IV, and ATP synthase (Xu et al, 2005a, Xu et al, 2005c). We also showed in our recent studies that caspase-3 activation was found in the fetal brains exposed prenatally to alcohol (Sari, 2009, Sari et al, 2009).…”

Section: Discussionmentioning

confidence: 64%

Activity-dependent neurotrophic factor-derived peptide prevents alcohol-induced apoptosis, in part, through Bcl2 and c-Jun N-terminal kinase signaling pathways in fetal brain of C57BL/6 mouse

Sari

Weedman

2012

Neuroscience

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Fetal alcohol exposure is known to induce alteration in fetal brain development. In this study, we focused on neuroprotection against the effects of alcohol exposure using ADNF-9, a peptide derived from activity-dependent neurotrophic factor. We used a mouse model of fetal alcohol exposure to identify the intracellular mechanisms underlying the neuroprotective effects of ADNF-9. On embryonic day 7 (E7), weight-matched pregnant females were assigned to the following groups: (1) ethanol liquid diet (ALC) of 25% (4.49%, v/v) ethanol derived calories; (2) pair-fed control (PF); (3) ALC combined with administration (i.p.) of ADNF-9 (ALC/ADNF-9); and (4) pair-fed combined with administration (i.p.) of ADNF-9 (PF/ADNF-9). On E13, fetal brains were collected, weighed, and apoptosis was determined using TUNEL assay. Bcl2 protein and phospho-c-Jun N-terminal kinase (JNK) levels were determined using Western blot and enzyme immunometric assay, respectively. ADNF-9 administration significantly prevented alcohol-induced reductions in fetal brain weight. In addition, ADNF-9 prevented an alcohol-induced increase in cell death in the primordium of the cerebral cortex and ganglionic eminence. Western blot analysis of the mitochondrial protein fractions revealed that ADNF-9 administration prevented an alcohol-induced reduction in the Bcl2 level. Moreover, an analysis of the proteins in the upstream signaling pathway revealed that ADNF-9 down-regulated the phosphorylation of JNK. These data indicate that the mitochondrial Bcl2 pathway and JNK upstream signaling pathway are the intracellular targets of ADNF-9. The neuroprotective mechanism of action of ADNF-9 provides a direction for potential therapeutics against alcohol-induced neural damage involving mitochondrial dysfunction.

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“…In this respect, it appears that while some sialic acids have a normal function inside the nucleus of dental cells, their presence is altered under experimental conditions. The mitochondria (Matthiessen and Romert, 1988;Xu et al, 2005), cytoskeleton (Azorin et al, 2001), endoplasmic reticulum (Matthiessen and Romert, 1983), and Golgi apparatus, as well as the enzymes associated with glycosylation, are altered by ethanol exposure during development (Renau-Piqueras et al, 1987Estrada et al, 1996). Previous reports demonstrated that some glycoproteins may be affected in fetal mice exposed to ethanol .…”

Section: Discussionmentioning

confidence: 97%

Alteration of the sialylation pattern of the murine tooth germ after ethanol exposure

Jiménez-Farfán

Guevara

Zenteno

et al. 2005

Birth Defects Research

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Impaired development of mitochondria plays a role in the central nervous system defects of fetal alcohol syndrome

Abstract: Impaired mitochondria development plays a role in the CNS defects induced by prenatal alcohol exposure.

Cited by 37 publications

References 65 publications

Ethanol Dose- and Time-dependently Increases α and β Subunits of Mitochondrial ATP Synthase of Cultured Neonatal Rat Cardiomyocytes

Ethanol Dose- and Time-dependently Increases α and β Subunits of Mitochondrial ATP Synthase of Cultured Neonatal Rat Cardiomyocytes

Activity-dependent neurotrophic factor-derived peptide prevents alcohol-induced apoptosis, in part, through Bcl2 and c-Jun N-terminal kinase signaling pathways in fetal brain of C57BL/6 mouse

Alteration of the sialylation pattern of the murine tooth germ after ethanol exposure

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