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1.
Artículo en Inglés | MEDLINE | ID: mdl-38664127

RESUMEN

BACKGROUND AND AIMS: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. METHODS AND RESULTS: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. CONCLUSION: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.

2.
Cell Cycle ; : 1-13, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38626328

RESUMEN

The precise mechanisms underlying the inhibitory effects of SIRT3, a mitochondrial sirtuin protein, on hepatocellular carcinoma (HCC) development, as well as its impact on mitochondrial respiration, remain poorly understood. We assessed sirtuins 3 (SIRT3) levels in HCC tissues and Huh7 cells cultured under hypoxic condition. We investigated the effects of SIRT3 on cell proliferation, glycolytic metabolism, mitochondrial respiration, mitophagy, and mitochondrial biogenesis in Huh7 cells. Besides, we explored the potential mechanisms regulating SIRT3 expression in hypoxically cultured Huh7 cells. Gradual reduction in SIRT3 expressions were observed in both adjacent tumor tissues and tumor tissues. Similarly, SIRT3 expressions were diminished in Huh7 cells cultured under hypoxic condition. Forced expression of SIRT3 attenuated the growth of hypoxically cultured Huh7 cells. SIRT3 overexpression led to a decrease in extracellular acidification rate while increasing oxygen consumption rate. SIRT3 downregulated the levels of hexokinase 2 and pyruvate kinase M2. Moreover, SIRT3 enhanced mitophagy signaling, as indicated by mtKeima, and upregulated key proteins involved in various mitophagic pathways while reducing intracellular reactive oxygen species levels. Furthermore, SIRT3 increased proxisome proliferator-activated receptor-gamma coactivator 1α levels and the amount of mitochondrial DNA in Huh7 cells. Notably, ß-catenin expressions were elevated in Huh7 cells cultured under hypoxic condition. Antagonists and agonists of ß-catenin respectively upregulated and downregulated SIRT3 expressions in hypoxically cultured Huh7 cells. The modulationsof glycolysis and mitochondrial respiration represent the primary mechanism through which SIRT3, suppressed by ß-catenin, inhibits HCC cell proliferation.

3.
Acta Cardiol ; : 1-9, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38469674

RESUMEN

BACKGROUND: The potential influence of tinnitus on cardiovascular disease (CVD) and all-cause mortality has yet to be explored. We aim to examine the correlations between tinnitus and the risk of cardiovascular events and all-cause mortality. METHODS: We conducted a prospective cohort study utilising data from the UK Biobank. The presence of tinnitus was evaluated through a questionnaire. The primary outcome was defined as a composition of cardiovascular events, including myocardial infarction (MI), stroke, and mortality from CVD, as well as all-cause mortality. Cox proportional hazard models were employed to examine the associations between tinnitus and both the primary outcome and its individual components. Sensitivity analyses were conducted to evaluate the robustness of the primary analysis. RESULTS: A total of 140,146 participants were included in the study. The presence of tinnitus was found to be associated with a higher incident rate of the primary outcome (HR = 1.057, 95%CI: 1.017-1.099, p = 0.005), MI (HR = 1.139, 95%CI: 1.061-1.222, p < 0.001) and all-cause mortality (HR = 1.053, 95%CI: 1.003-1.105, p = 0.038) after adjusting for confounders. However, there was no significant association between tinnitus and stroke or mortality from CVD. Subgroup analysis revealed that the association between tinnitus and the primary outcome was significant in females, participants with abnormal BMI, and those without hearing difficulty, depression or anxiety. Sensitivity analyses yielded consistent results. CONCLUSION: The findings from this study contribute to the existing body of evidence suggesting an association between tinnitus and an increased risk of cardiovascular events and all-cause mortality.

4.
Heart Rhythm ; 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38336194

RESUMEN

BACKGROUND: Emerging evidence has linked daytime napping with the risk of cardiovascular events. Cardiac arrhythmias are considered an early clinical stage for cardiovascular diseases. However, whether napping frequency is associated with incident arrhythmias remains unknown. OBJECTIVE: This study aimed to prospectively investigate the association between napping frequency and cardiac arrhythmias. METHODS: Daytime napping frequency was self-reported in response to touchscreen questionnaires. The primary outcomes were incident arrhythmias including atrial fibrillation/flutter (AF/Af), ventricular arrhythmia, and bradyarrhythmia. Cox regression analysis was conducted on the basis of 491,117 participants free of cardiac arrhythmias from the UK Biobank. The 2-sample mendelian randomization (MR) and 1-sample MR were used to ensure a causal effect of genetically predicted daytime napping on the risk of arrhythmias. RESULTS: During a median follow-up of 11.91 years, 28,801 incident AF/Af cases, 4132 incident ventricular arrhythmias, and 11,616 incident bradyarrhythmias were documented. Compared with never/rarely napping, usually napping was significantly associated with higher risks of AF/Af (hazard ratio, 1.141; 95% CI, 1.083-1.203) and bradyarrhythmia (hazard ratio, 1.138; 95% CI, 1.049-1.235) but not ventricular arrhythmia after adjustment for various covariates. The 2-sample MR and 1-sample MR analysis showed that increased daytime napping frequency was likely to be a potential causal risk factor for AF/Af in FinnGen (odds ratio, 1.626; 95% CI, 1.061-2.943) and bradyarrhythmia in the UK Biobank (odds ratio, 1.005; 95% CI, 1.002-1.008). CONCLUSION: The results of this study add to the burgeoning evidence of an association between daytime napping frequency and an increased risk of cardiac arrhythmias including AF/Af, ventricular arrhythmia, and bradyarrhythmia.

5.
Hypertens Res ; 47(5): 1157-1166, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38212367

RESUMEN

Remnant cholesterol (RC) has been associated with atherosclerotic cardiovascular disease, but its relationship with hypertension remains unclear. This prospective cohort study aimed to investigate the association between RC and subsequent hypertension risk. Data from the UK Biobank, comprising 295,062 participants initially free of hypertension, were analyzed. Cox proportional hazards regression assessed the association between RC quartiles and hypertension risk. Discordance analysis evaluated the risk of hypertension in discordant/concordant groups of RC and low-density lipoprotein cholesterol (LDL-C) using the difference in percentile units (>10 units). Restricted cubic spline curves were used to model the relationship between RC and hypertension risk. The mean ± SD age of participants was 55.1 ± 8.1 years, with 40.6% being men and 94.7% White. During a median follow-up of 12.8 years, 39,038 participants developed hypertension. Comparing extreme quartiles of RC, the hazard ratio (HR) for incident hypertension was 1.20 (95% CI: 1.17-1.24). After adjusting for traditional risk factors, each 1 mmol/L increase in RC levels was associated with a 27% higher risk of incident hypertension (HR: 1.27; 95% CI: 1.23-1.31). The discordant group with high RC/low LDL-C exhibited a higher risk of incident hypertension compared to the concordant group (HR: 1.06; 95% CI: 1.03-1.09). Spline curves further demonstrated a positive association between RC and the risk of incident hypertension. We concluded that elevated RC emerged as an independent risk factor of incident hypertension, extending beyond traditional risk factors. Monitoring RC levels and implementing interventions to lower RC may have potential benefits in preventing hypertension.


Asunto(s)
Colesterol , Hipertensión , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Femenino , Estudios Prospectivos , Colesterol/sangre , Adulto , Factores de Riesgo , Incidencia , LDL-Colesterol/sangre , Anciano , Reino Unido/epidemiología , Estudios de Cohortes
6.
Sci Data ; 11(1): 117, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38267446

RESUMEN

The giant ladybug Megalocaria dilatata (Fabricius) is a potential biocontrol agent and a valuable model for coccinellid genomics and evolutionary biology. However, the lack of a reference genome for M. dilatata has impeded further explorations into its evolution and constrained its use in pest management. Here, we assembled and annotated a high-quality, chromosome-level genome of M. dilatata. The resulting assembly spans 772.3 Mb, with a scaffold N50 of 72.48 Mb and a GC content of 34.23%. The Hi-C data aided in anchoring the assembly onto 10 chromosomes ranging from 43.35 to 108.16 Mb. We identified 493.33 Mb of repeat sequences, accounting for 63.88% of the assembled genome. Our gene prediction identified 25,346 genes, with 81.89% annotated in public protein databases. The genome data will provide a valuable resource for studying the biology and evolution of Coccinellidae, aiding in pest control strategies and advancing research in the field.


Asunto(s)
Escarabajos , Genoma de los Insectos , Animales , Cromosomas , Bases de Datos de Proteínas , Genómica
7.
Diabetes Metab ; 49(5): 101472, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37678759

RESUMEN

AIM: To examine the associations between serum albumin and the incidences of diabetes and diabetic microvascular complications in participants of the UK Biobank cohort. METHODS: There were 398,146 participants without diabetes and 30,952 patients with diabetes from the UK Biobank cohort included in this study. Multivariate-adjusted Cox proportional hazard models were used to analyze the association of albumin with the incidences of diabetes and diabetic microvascular complications. Mendelian randomization (MR) analysis was used to determine the genetic relationships between serum albumin and diabetes. RESULTS: After a median 12.90 years follow-up, 14,710 participants developed incident diabetes (58.83 ± 7.52 years, 56.10% male). After multivariate adjustment, serum albumin was inversely associated with incident diabetes: hazard ratio (HR) [95% confidence interval] per 10 g/l increase 0.88 [0.82;0.94]. MR analyses suggested a potential genetic influence of serum albumin on diabetes in both the UK Biobank and the FinnGen consortium: odds ratios (ORs) [95% confidence interval per 1 g/l increase 0.99 [0.98;1.00] and 0.78 [0.67;0.92], respectively. In patients with diabetes, higher serum albumin levels were significantly associated with lower risk for diabetic microvascular complications. Specifically, per 10 g/l increase in serum albumin, the HRs for diabetic nephropathy, ophthalmopathy, and neuropathy were 0.42 [0.30;0.58], 0.61 [0.52;0.72], and 0.67 [0.51;0.88], respectively. CONCLUSION: In this large prospective study, serum levels of albumin were inversely associated with the incidences of diabetes and diabetic microvascular complications. These findings underscore the importance of maintaining optimal nutrient status in reducing the risk of diabetes and its complications.


Asunto(s)
Diabetes Mellitus Tipo 2 , Angiopatías Diabéticas , Nefropatías Diabéticas , Humanos , Masculino , Femenino , Estudios Prospectivos , Albúmina Sérica , Bancos de Muestras Biológicas , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/complicaciones , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/genética , Angiopatías Diabéticas/complicaciones , Reino Unido/epidemiología , Factores de Riesgo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética
8.
Biodivers Data J ; 11: e104618, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37332536

RESUMEN

Background: The taeniopterygid genus Taenionema Banks, 1905 currently contains 14 species distributed in the Nearctic and the eastern Palearctic Regions. Taenionemajaponicum (Okamoto, 1922) is the only species known from the Eastern Hemisphere, specifically in Japan, Korea, Mongolia, Russia and north-eastern China. The authors recently described the larvae of an undetermined Taenionema species, which was supposed to represent a second Palaearctic species. New information: This paper reports the first endemic species of Taenionema Banks, 1905, Taenionemasinensis sp. n. from China, which also represents the second species of Taenionema from the Eastern Hemisphere. Description and illustrations based on male and female adults are provided. The new species is easily distinguished from all congeners by the bilobed abdominal sternum 9 of the male adult. The female adult is characterised by the posteriorly truncate postgenital plate. The male larva is distinguished by the emarginate subgenital plate and hook-shaped paraprocts.

9.
Zootaxa ; 5244(4): 361-376, 2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-37044456

RESUMEN

The stoneflies are a relatively ancient group of aquatic insects. The larvae of stoneflies are exclusively aquatic and are important bioindicators for water quality changes. However, the identification and classification of stonefly larvae are much more difficult than the adults, due to the lack of sufficient descriptions for most stonefly taxa. Styloperlidae is an endemic stonefly family in South Asia. The larval morphology of this family remains less clear in comparison with their adults. In this paper, the larvae of Styloperla inae Chao, 1947 and Cerconychia flectospina Wu, 1962 are described and illustrated based on specimens from China. Their morphology corresponds with the proposed diagnostic larval characters of Styloperlidae in previous studies. Additional auxiliary characters useful for the identification of larvae in Styloperlidae are discussed. The larvae of S. inae and C. flectospina exhibit subtle morphological differences but can be easily distinguished by the presence or absence of dark sclerites on all the thoracic sternal pits.


Asunto(s)
Insectos , Neoptera , Animales , Larva , China
10.
Genes (Basel) ; 13(10)2022 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-36292766

RESUMEN

Anoplophora glabripennis (Motschulsky, 1854) and Demonax pseudonotabilis Gressitt & Rondon, 1970 are two commonly found longicorn beetles from China. However, the lack of sufficient molecular data hinders the understanding of their evolution and phylogenetic relationships with other species of Cerambycidae. This study sequenced and assembled the complete mitochondrial genomes of the two species using the next-generation sequencing method. The mitogenomes of A. glabripennis and D. pseudonotabilis are 15,622 bp and 15,527 bp in length, respectively. The mitochondrial gene content and gene order of A. glabripennis and D. pseudonotabilis are highly conserved with other sequenced longicorn beetles. The calculation of nonsynonymous (Ka) and synonymous (Ks) substitution rates in PCGs indicated the existence of purifying selection in the two longicorn beetles. The phylogenetic analysis was conducted using the protein-coding gene sequences from available mitogenomes of Cerambycidae. The two species sequenced in this study are, respectively, grouped with their relatives from the same subfamily. The monophyly of Cerambycinae, Dorcasominae, Lamiinae, and Necydalinae was well-supported, whereas Lepturinae, Prioninae, and Spondylidinae were recovered as paraphyletic.


Asunto(s)
Escarabajos , Genoma Mitocondrial , Animales , Escarabajos/genética , Filogenia , Genes Mitocondriales , China
11.
Biology (Basel) ; 11(6)2022 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-35741328

RESUMEN

Haplodiplatyidae is a recently established earwig family with over 40 species representing a single genus, Haplodiplatys Hincks, 1955. The morphology of Haplodiplatyidae has been studied in detail, but its molecular characters remain unclear. In this study, two mitogenomes of Haplodiplatys aotouensis Ma & Chen, 1991, were sequenced based on two samples from Fujian and Jiangxi provinces, respectively. These represent the first mitogenomes for the family Haplodiplatyidae. The next-generation sequencing method and subsequent automatic assembly obtained two mitogenomes. The two mitogenomes of H. aotouensis were generally identical but still exhibit a few sequence differences involving protein-coding genes (PCGs), ribosomal RNA (rRNA) genes, control regions, and intergenic spacers. The typical set of 37 mitochondrial genes was annotated, while many transfer RNA (tRNA) genes were rearranged from their ancestral locations. The calculation of nonsynonymous (Ka) and synonymous (Ks) substitution rates in PCGs indicated the fastest evolving nd4l gene in H. aotouensis. The phylogenetic analyses supported the basal position of Apachyidae but also recovered several controversial clades.

12.
Zootaxa ; 5115(4): 559-570, 2022 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-35391351

RESUMEN

A new species of Zapada Ricker, 1952, Zapada kondratieffi sp. nov. from central Sichuan Province of China is described and illustrated, which represents the first record of the genus in China. The new species is characterized mainly by the presence of five simple cervical gills, vestigial inner paraproct lobe, and absence of paraproct spines. The preliminary molecular phylogenetic analysis using COI sequences recovered the relationship among eight species of Zapada and supports the close relationship between Z. kondratieffi and Zapada frigida (Claassen, 1923).


Asunto(s)
Insectos , Neoptera , Distribución Animal , Animales , China , Filogenia
13.
Zookeys ; 1087: 105-122, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35437361

RESUMEN

The phylogenetic position and inner relationships of Dermaptera remain unresolved despite the numerous efforts using morphological and molecular data. To facilitate the resolution of problems, this study sequenced the complete mitogenome of Apachyusfeae de Bormans, 1894 (Apachyidae) and the nearly complete mitogenome of Diplatysflavicollis Shiraki, 1907 (Diplatyidae). The 19,029-bp long mitogenome of A.feae exhibited an extra trnV gene and two control regions in addition to the typical set of 37 genes including 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, and two ribosomal RNA (rRNA) genes. The 12,950-bp long partially sequenced mitogenome of D.flavicollis was composed of 10 and a partial fragment of PCGs, 18 tRNA genes, two rRNA genes, and a control region. Comparative analysis of available earwig mitogenomes revealed variable mitogenomic structure and extensive gene rearrangements in Dermaptera. The preliminary phylogenetic analyses using Bayesian inference and maximum likelihood methods showed identical results, but the limited sampling and different types of molecular data lead to an apparent incongruence with previous phylogenetic studies.

14.
Biodivers Data J ; 10: e87247, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36761635

RESUMEN

Background: Perlodinella Klapálek, 1912 is a small stonefly genus in the Palearctic areas of China and its biodiversity is underestimated. New information: This paper reports a new species of Perlodinella, Perlodinellashennongjia sp. nov. in the Dajiuhu National Wetland Park of Shennongjia Forestry District, Hubei Province, central China. The description and illustrations of the new species are provided, based on male adults, female adults and eggs. The new species can be distinguished from its congeners by the characters of male and female genitalia and the egg structure.

15.
Zootaxa ; 5213(2): 190-198, 2022 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-37044942

RESUMEN

Aposthonia guizhouensis sp. nov. from Guizhou Province of China is described and illustrated. The new species is characterized by the distinctive terminalia structure in males. Aposthonia guizhouensis sp. nov. represents the second species of Aposthonia known from China. DNA barcode of the new species is sequenced and compared with its related congeners.


Asunto(s)
Insectos , Neoptera , Masculino , Animales , Insectos/genética , Secuencia de Bases , China , Distribución Animal
16.
Zootaxa ; 5061(3): 573-583, 2021 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-34810607

RESUMEN

Microperla retroloba (Wu, 1937) is a poorly described species from Gansu Province of China and the types of which were apparently lost. Herein, a neotype of M. retroloba is designated based on new material from Ningxia Hui Autonomous Region adjacent to Gansu Province. Male, female, larva and egg morphology of M. retroloba are described, illustrated and compared with all congeners.


Asunto(s)
Neoptera , Animales , Femenino , Larva , Masculino
17.
Zootaxa ; 5027(2): 160-174, 2021 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-34811236

RESUMEN

A remarkable new species of Isoperla Banks, 1906, Isoperla chongxui sp. nov. from Henan Province of China is described and illustrated. The new species is characterized by the conspicuous abdominal tergal processes in males. Comparisons are made between the new species and its congeners. New descriptions and illustrations are provided for Isoperla kozlovi Zhiltzova, 1972 from northeastern China. Isoperla fengi Wu Claassen, 1934 and Isoperla curvispina (Wu, 1938) are considered nomen dubia due to lost types and poor original descriptions.


Asunto(s)
Insectos , Neoptera , Distribución Animal , Animales , China , Masculino
18.
Mitochondrial DNA B Resour ; 6(12): 3400-3401, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34790874

RESUMEN

The complete mitochondrial genome of the perlodid stonefly, Filchneria songi Chen, 2019 was sequenced and analyzed. This double strand, circular molecule is 16,028 bp in length with an A + T content of 70.1%, and contains 13 PCGs, 22 tRNA genes, and two rRNA genes. A 1099-bp long control region was detected, with a high A + T content of 81.9%. Gene arrangement was conserved in the mitogenome of F. songi. Most PCGs use standard start codons and ended with complete stop codons. The phylogenetic analysis supported that F. songi was closely related with species of Perlodes Banks, 1903.

19.
Front Cardiovasc Med ; 8: 701745, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34660710

RESUMEN

Objective: To explore the role of glycolysis in cardiac fibroblast (CF) activation and cardiac fibrosis after myocardial infarction (MI). Method: In vivo: 2-Deoxy-D-glucose (2-DG), a glycolysis inhibitor, was injected into the abdominal cavity of the MI or sham mice every day. On the 28th day, cardiac function was measured by ultrasonic cardiography, and the hearts were harvested. Masson staining and immunofluorescence (IF) were used to evaluate the fibrosis area, and western blot was used to identify the glycolytic level. In vitro, we isolated the CF from the sham, MI and MI with 2-DG treatment mice, and we also activated normal CF with transforming growth factor-ß1 (TGF-ß1) and block glycolysis with 2-DG. We then detected the glycolytic proteins, fibrotic proteins, and the concentrations of lactate and glucose in the culture medium. At last, we further detected the fibrotic and glycolytic markers in human fibrotic and non-fibrotic heart tissues with masson staining, IF and western blot. Result: More collagen and glycolytic protein expressions were observed in the MI mice hearts. The mortality increased when mice were treated with 2-DG (100 mg/kg/d) after the MI surgery (Log-rank test, P < 0.05). When the dosage of 2-DG declined to 50 mg/kg/d, and the treatment was started on the 4th day after MI, no statistical difference of mortality between the two groups was observed (Log-rank test, P = 0.98). The collagen volume fraction was smaller and the fluorescence signal of α-smooth muscle actin (α-SMA) was weaker in mice treated with 2-DG than PBS. In vitro, 2-DG could significantly inhibit the increased expression of both the glycolytic and fibrotic proteins in the activated CF. Conclusion: Cardiac fibrosis is along with the enhancement of CF activation and glycolysis. Glycolysis inhibition can alleviate cardiac fibroblast activation and cardiac fibrosis after myocardial infarction.

20.
Cell Death Dis ; 12(6): 557, 2021 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-34050133

RESUMEN

Maintaining proper mitochondrial respiratory function is crucial for alleviating cardiac metabolic disorders during obesity, and mitophagy is critically involved in this process. Long non-coding RNA H19 (H19) is crucial for metabolic regulation, but its roles in cardiac disorders, mitochondrial respiratory function, and mitophagy during obesity are largely unknown. In this study, palmitic acid (PA)-treated H9c2 cell and Lep-/- mice were used to investigate cardiac metabolic disorders in vitro and in vivo, respectively. The effects of H19 on metabolic disorders, mitochondrial respiratory function, and mitophagy were investigated. Moreover, the regulatory mechanisms of PA, H19, mitophagy, and respiratory function were examined. The models tested displayed a reduction in H19 expression, respiratory function and mitochondrial number and volume, while the expression of mitophagy- and Pink1/Parkin signaling-related proteins was upregulated, as indicated using quantitative real-time PCR, Seahorse mitochondrial stress test analyzer, transmission electron microscopy, fluorescence indicators and western blotting. Forced expression of H19 helped to the recoveries of respiratory capacity and mitochondrial number while inhibited the levels of mitophagy- and Pink1/Parkin signaling-related proteins. Pink1 knockdown also attenuated PA-induced mitophagy and increased respiratory capacity. Mechanistically, RNA pull-down, mass spectrometry, and RNA-binding protein immunoprecipitation assays showed that H19 could hinder the binding of eukaryotic translation initiation factor 4A, isoform 2 (eIF4A2) with Pink1 mRNA, thus inhibiting the translation of Pink1 and attenuation of mitophagy. PA significantly increased the methylation levels of the H19 promoter region by upregulation Dnmt3b methylase levels, thereby inhibiting H19 transcription. Collectively, these findings suggest that DNA methylation-mediated the downregulation of H19 expression plays a crucial role in cardiomyocyte or H9c2 cells metabolic disorders and induces cardiac respiratory dysfunction by promoting mitophagy. H19 inhibits excessive mitophagy by limiting Pink1 mRNA translation, thus alleviating this cardiac defect that occurs during obesity.


Asunto(s)
Mitocondrias/metabolismo , Mitofagia/genética , Obesidad/genética , ARN Largo no Codificante/genética , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Regulación hacia Abajo , Humanos , Ratones , Obesidad/patología , Ratas , Smegmamorpha , Transfección
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