Effect of Ethanol on Gene Expression of Beating Neonatal Rat Cardiomyocytes - Further Research with Ingenuity Pathway Analysis Software -

Mashimo, Keiko; Ohno, Youkichi

doi:10.1272/jnms.jnms.2021_88-501

Cited by 5 publications

(11 citation statements)

References 30 publications

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“…A recent study on the prognosis markers of glioblastoma revealed the expression of ASIC5 as associated prognosis markers (55). ASIC5 was found to be activated in the ethanol-(100 mM)-exposed neonatal rat cardiomyocytes along with other six molecules (CYP2A6, PRL, CHRNA4, CNR1, CRH, and SLC40A1) (56). Low (in 50%) ASIC5 protein expression in melanoma were observed with <4% mutation rates (57).…”

Section: Discussionmentioning

confidence: 97%

Whole-Genome Sequencing Reveals Exonic Variation of ASIC5 Gene Results in Recurrent Pregnancy Loss

et al. 2021

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Family trio next-generation sequencing-based variant analysis was done to identify the genomic reason on unexplained recurrent pregnancy loss (RPL). A family (dead fetus and parents) from Saudi Arabia with an earlier history of three unexplained RPLs at the ninth week of pregnancy was included in the study. Whole-genome sequencing (WGS) of a dead fetus and the parents was done to identify the pathogenic variation and confirmed through Sanger sequencing. WGS of dead fetus identifies a novel homozygous exonic variation (NM_017419.3:c.680G>T) in ASIC5 (acid-sensing ion channel subunit family member 5) gene; the parents are heterozygous. Newly designed ARMS PCR followed by direct sequencing confirms the presence of heterozygous in one subject and absence of homozygous novel mutation among randomly selected healthy Saudis. The second family with heterozygous was confirmed with three unexplained RPLs. Pathogenicity analysis of R227I amino acid substitution in ASIC5 protein through molecular docking and interaction analysis revealed that the mutations are highly pathogenic, decrease the stability of the protein, and prevent binding of amiloride, which is an activator to open the acid-sensing ion channel of ASIC5. The identified rare and novel autosomal recessive mutation, c.680G>T:p.R227I (ASIC5Saudi), in two families confirm the ASIC5 gene association with RPL and can be fatal to the fetus.

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Section: Discussionmentioning

confidence: 97%

Whole-Genome Sequencing Reveals Exonic Variation of ASIC5 Gene Results in Recurrent Pregnancy Loss

et al. 2021

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“…Попередні дослідження показали, що аутофагія також може бути механізмом кардіотоксичності етанолу за рахунок протеїнкінази, активованої аденозинмонофосфатом, з подальшим ушкодженням метаболізму глюкози та ліпідів [11]. У морфологічних і молекулярно-біологічних дослідженнях доведено, що тривала дія етанолу пригнічує синтез і викликає деградацію структурних білків кардіоміоцитів, особливо білків міофібрил -актину, міозину, тітину, небуліну, тропоніну, тропоміозину [4,16,21]. Це призводить до ушкодження міофібрил, їх стоншення, дезорієнтації, втрати цілісності, спотворення конфігурації телофрагм та вставних дисків [2,16].…”

Section: вступunclassified

“…У морфологічних і молекулярно-біологічних дослідженнях доведено, що тривала дія етанолу пригнічує синтез і викликає деградацію структурних білків кардіоміоцитів, особливо білків міофібрил -актину, міозину, тітину, небуліну, тропоніну, тропоміозину [4,16,21]. Це призводить до ушкодження міофібрил, їх стоншення, дезорієнтації, втрати цілісності, спотворення конфігурації телофрагм та вставних дисків [2,16]. Показано, що в кардіоміоцитах за умов дії етанолу можна визначити міофібрили як у релаксованому, так і в надмірно скороченому стані [6,22].…”

Section: вступunclassified

“…Серцеві міоцити можуть розвивати функціональний і структурний компенсаторні механізми, здатні мінімізувати або відновити спричинене етанолом пошкодження. Зокрема, на ранніх етапах хронічної алкоголізації спостерігається клітинна гіпертрофія для компенсації скоротливої дисфункції, проте тривалий вплив етанолу призводить до незворотних процесів у структурі та функціонуванні кардіоміоцитів, причому найчутливішими до токсичної дії алкоголю внутрішньоклітинними органелами є міофібрили та мітохондрії [6,16].…”

Section: вступunclassified

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Ultrastructural Features of Cardiomyocyte Contractile Apparatus in Rat Offspring Hearts Following Maternal Chronic Alcohol Intoxication

Tverdokhlib,

Marchenko

2024

Med. and Ecol. probl.

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Background. The mechanisms underlying the development of the heart contractile apparatus and the distribution of myofibrils in cardiomyocytes following intrauterine ethanol intoxication continue to be a topic of significant debate. The aim of this paper is to determine the dynamics of postnatal changes in the ultrastructure of ventricular contractile cardiomyocytes in the rat heart after chronic alcoholization of the maternal organism. Methods. The study focused on the hearts of rat offspring from birth to adulthood. Transmission electron microscopy was utilized to examine the ultrastructure of cardiomyocytes in various zones of the ventricular myocardium. Results. It has been observed that prenatal alcohol exposure induces cardiomyocyte heteromorphism, characterized by varying degrees of damage throughout postnatal ontogenesis in rat offspring. Specifically, cells exhibiting critical signs of destruction in the myocardium of intramural and subepicardial zones of both ventricles aggregate into clusters surrounded by morphologically intact cardiomyocytes, while irreversibly damaged cells with subendocardial localization appear isolated. Following birth, there is a progressive accumulation of mitochondria exhibiting signs of limited functional activity. These polymorphic organelles, featuring a matrix of moderate or low electron density with sporadically developed cristae, primarily concentrate in paranuclear regions and are dispersed along the interstices of myofibril dissociation. Conclusion. Maternal chronic alcohol intoxication results in enduring harm to the contractile apparatus of ventricular cardiomyocytes in rat offspring. This damage manifests as sarcomere structure disorganization, myofibril fragmentation and misalignment, notable suppression of sarcomerogenesis, and reduced myofibril content, all closely linked to mitochondrial alterations.

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“…Ingenuity pathway analysis (IPA) is a powerful tool with multipurpose solutions for the interpretation, and the analysis of complicated experimental datasets ( 8 ). It has also been used by many scientific research institutions ( 9 ), including medical, pharmaceutical, and biotechnological institutions, among others. Based on this, iTRAQ quantitative proteomics associated with IPA analytical tool can offer a credible biological analysis of RA ( 10 ) by comparing different groups, especially could help us to reveal the key up-regulated or down-regulated DEPs.…”

Section: Introductionmentioning

confidence: 99%

The mechanism of the anti-inflammatory effect of Oldenlandia diffusa on arthritis model rats: a quantitative proteomic and network pharmacologic study

Zhu¹,

Xiong²,

Lü³

et al. 2022

Ann Transl Med

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Background: In China, Oldenlandia diffusa (OD) has been prescribed as a therapeutic herb for rheumatoid arthritis (RA). We previously conducted a preliminary study of the anti-inflammatory effect of OD, and the purpose of this study is to further investigate its mechanism.Methods: We performed a quantitative proteomic analysis of synovium, identified the differentially expressed proteins, and performed bioinformatics analyses. With the help of network pharmacology, we aimed to find the key synovial proteins which OD or its key compound might influence. To verify the result, liquid chromatography-mass spectrometry (LC-MS) was applied to quantify and qualify the absorbable potential compounds of OD. The anti-inflammatory effect was evaluated by morphological, histopathological, and cytokine analyses. Target proteins were observed by immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA).Results: MMP3 and CAV1 were identified as 2 of the differentially expressed proteins in RA synovium, and might be influenced by quercetin, the active compound of OD. MMP3 might be altered through atherosclerosis signaling, while CAV1 might be altered through caveolar-mediated endocytosis signaling. According to our verification, quercetin was identified as the absorbed and effective compound of OD, and it could exert an anti-inflammatory effect on the collagen induced arthritis (CIA) model, including serum cytokine expression, synovial hyperplasia and lymphocyte infiltration, articular cartilage lesion. Quercetin could also down-regulate the synovial expression of MMP3 and CAV1, and could exert better effects at a high dose.Conclusions: Quercetin was the main active compound of OD in the treatment of RA. OD might alleviate inflammatory responses in CIA rats by suppressing the expression of MMP3 and CAV1 through quercetin, and at a high dose, quercetin could exert a better anti-inflammatory effect.

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Effect of Ethanol on Gene Expression of Beating Neonatal Rat Cardiomyocytes - Further Research with Ingenuity Pathway Analysis Software -

Cited by 5 publications

References 30 publications

Whole-Genome Sequencing Reveals Exonic Variation of ASIC5 Gene Results in Recurrent Pregnancy Loss

Whole-Genome Sequencing Reveals Exonic Variation of ASIC5 Gene Results in Recurrent Pregnancy Loss

Ultrastructural Features of Cardiomyocyte Contractile Apparatus in Rat Offspring Hearts Following Maternal Chronic Alcohol Intoxication

The mechanism of the anti-inflammatory effect of Oldenlandia diffusa on arthritis model rats: a quantitative proteomic and network pharmacologic study

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