HAPLN1 knockdown inhibits heart failure development via activating the PKA signaling pathway

BMC Cardiovascular Disorders, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 5, 2024

Abstract Background Heart failure (HF) is a heterogeneous syndrome that affects millions worldwide, resulting in substantial health and economic burdens. However, the molecular mechanism of HF pathogenesis remains unclear. Methods HF-related key genes were screened by bioinformatics approach.The impacts HAPLN1 knockdown on Angiotensin II (Ang II)-induced AC16 cells assessed through series cell function experiments. Enzyme-linked immunosorbent assay (ELISA) was used to measure levels oxidative stress apoptosis-related factors. The rat model induced subcutaneous injection isoprenaline histopathologic changes cardiac tissue hematoxylin eosin (HE) staining echocardiographic index. Downstream pathways regulated predicted then confirmed vivo vitro western blot. Results Six hub screened, which HAPLN1, FMOD, NPPB, NPPA, COMP overexpressed, whereas NPPC downregulated HF. Further research found silencing promoted viability reduced apoptosis Ang II-induced cells. left ventricular ejection fraction (LVEF) shortening (LVFS), while decreasing end-systolic volume (LVESV) model. GSH suppressed MDA, LDH, TNF-α, IL-6. Mechanistically, activated PKA pathway, both vitro. Conclusion inhibited progression activating may provide novel perspectives management

Language: Английский

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The role of serine/threonine protein kinases in cardiovascular disease and potential therapeutic methods

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 117093 - 117093

Published: July 5, 2024

Protein phosphorylation is an important link in a variety of signaling pathways, and most the life processes cells involve protein phosphorylation. Based on amino acid residues phosphorylated proteins, kinases can be categorized into following families: serine/threonine kinases, tyrosine-specific histidine-specific tryptophan aspartate/glutamyl kinases. Of all are where that catalyze serine or threonine target proteins using ATP as phosphate donor. The current socially accepted classification to divide them seven major groups: kinase A, G, C (AGC), CMGC, Calmodulin-dependent (CAMK), Casein (CK1), STE, Tyrosine (TKL) others. After decades research, preliminary understanding specific respective functions has entered new period exploration. In this paper, we review literature previous years introduce pathways related therapeutic modalities played by each small family, respectively, some common cardiovascular system diseases such heart failure, myocardial infarction, ischemia-reperfusion injury, diabetic cardiomyopathy. To certain extent, research results, including molecular mechanisms methods, fully summarized systematic report made for prevention treatment future.

Language: Английский

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Downregulation of amphiregulin improves cardiac hypertrophy via attenuating oxidative stress and apoptosis

Biology Direct, Journal Year: 2022, Volume and Issue: 17(1)

Published: Aug. 22, 2022

Abstract Amphiregulin (AREG) is a ligand of epidermal growth factor receptor and participates in the fibrosis multiple organs. However, whether AREG can regulate hypertrophic cardiomyopathy not well known. This research aims to explore effect on cardiac hypertrophy, oxidative stress apoptosis was involved influence hypertrophy. Angiotensin (Ang) II induced hypertrophy mice neonatal rat cardiomyocytes (NRCMs) or HL-1 cells vitro. expressions raised heart mice. After downregulation, increases Ang weight area were inhibited. Down-regulation could inhibit atrial natriuretic peptide, brain beta-myosin heavy chain mice, NRCMs cells. The enhancement with treatment alleviated by knockdown. raises Bax cleaved caspase3 inhibited downregulation. downregulation reduced myocardial via inhibition apoptosis. may be target for future treatment.

Language: Английский

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Myocardial toxicity induced by silica nanoparticles in a transcriptome profile

Nanoscale, Journal Year: 2022, Volume and Issue: 14(16), P. 6094 - 6108

Published: Jan. 1, 2022

The deleterious effects of silica nanoparticles (SiNPs) on human health and the ecological system have gradually gained attention owing to their heavy annual output extensive global flux. updated epidemiological or experimental investigations demonstrated potential myocardial toxicity triggered by SiNPs, but underlying mechanisms long-lasting cardiac are still poorly understood. Here, a rat model sub-chronic respiratory exposure SiNPs was conducted, histopathological analysis ultrastructural investigation heart tissues were carried out. More importantly, comprehensive whole-genome transcription utilized in uncover key biological cellular SiNPs. widening space partial fiber rupture clearly manifested after prolonged exposure, particularly accompanied mitochondrial swelling cristae rupture. With aid Affymetrix GeneChips, 3153 differentially expressed genes (DEGs) identified including 1916 down- 1237 up-regulated genes. GO KEGG illustrated many important processes pathways perturbed mainly specializing stress, energy metabolism, actin filament dynamics immune response. Signal-net revealed that Prkaca (PKA) plays core role toxification process rats. Furthermore, qRT-PCR verified PKA-mediated calcium signaling is probably responsible for SiNPs-induced injury. Conclusively, our study caused injury, particularly, provided transcriptomic insight into PKA-calcium which would facilitate SiNPs-based nanosafety assessment biomedicine development.

Language: Английский

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Exogenous galanin alleviates hepatic steatosis by promoting autophagy via the AMPK-mTOR pathway

Archives of Biochemistry and Biophysics, Journal Year: 2023, Volume and Issue: 744, P. 109689 - 109689

Published: July 8, 2023

Language: Английский

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Alarin potentiates ongoing epileptiform activity in rat brain slices: an in vitro electrophysiological study

Acta Neurobiologiae Experimentalis, Journal Year: 2024, Volume and Issue: 84(1), P. 35 - 42

Published: Feb. 21, 2024

Alarin is a newly discovered neuropeptide that belongs to the galanin peptide family with wide range of bioactivity in nervous system. Its function brain's autonomic areas has been studied, and it reported alarin involved regulation excitability hypothalamic neurons. role hippocampus, however, unknown. In this study, we investigated if induced any synchronous discharges or epileptiform activity, had effect on already initiated discharges. We used thick acute horizontal hippocampal slices obtained from 30‑ 35‑day‑old rats. Extracellular field potential recordings were evaluated CA1 region hippocampus. Our data demonstrated that, application did not result activity abnormal 4‑aminopyridine was applied induce slices. found increased frequency interictal‑like events mean power local potentials which by 4‑aminopyridine. These results for first time modulatory synchronized neuronal showed contribution epilepsy‑like conditions.

Language: Английский

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Alarin potentiates ongoing epileptiform activity in rat brain slices: an in vitro electrophysiological study

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 9, 2023

Alarin is a newly discovered neuropeptide that belongs to the galanin peptide family and has wide range of bioactivity in nervous system. Its function brain's autonomic areas been studied, it reported involved regulation excitability hypothalamic neurons. role hippocampus, however, unknown. In this study, we investigated if alarin induced any synchronous discharges or epileptiform activity, effect on previously initiated discharges. We used 350 µm thick acute horizontal hippocampal slices obtained from 30- 35-day-old rats. Extracellular field potential recordings were evaluated hippocampus CA1 region. Our data demonstrated that, application did not initiate activity abnormal 4-Aminopyridine was applied induce slices. found 200 nM increased frequency interictal-like events mean power local potentials region which by 4-aminopyridine. These results exhibited for first time modulatory synchronized neuronal should be considered future therapeutic approaches.

Language: Английский

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Heart peptides and HFpEF (heart failure with preserved ejection fraction)

Peptides, Journal Year: 2022, Volume and Issue: 157, P. 170866 - 170866

Published: Sept. 5, 2022

Language: Английский

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