Dataset Information

Protective Effects of Nanoceria against Mitochondrial Dysfunction and Angiotensin II-Induced Hypertrophy in H9c2 Cardiomyoblasts.

ABSTRACT: Mitochondrial dysfunction triggered by increased reactive oxygen species (ROS) generation is involved in the pathogenesis and development of cardiac hypertrophy. Nanoceria (cerium oxide nanoparticle) has powerful ROS-scavenging properties and is considered a potential therapeutic option for curbing ROS-related disorders. Here, we explored the signaling mechanism underlying the protective effects of nanoceria against angiotensin (Ang) II-stimulated pathological response in H9c2 cardiomyoblasts. Our data revealed that pretreatment of H9c2 cardiomyoblasts with nanoceria significantly prevented Ang II-stimulated generation of intracellular ROS, aberrant expression of pro-inflammatory cytokines, and hypertrophy markers. Nanoceria pretreatment increased the mRNA levels of genes regulating the cellular antioxidant defense system (SOD2, MnSOD, CAT) in Ang II-treated cells. Furthermore, nanoceria restored mitochondrial function by decreasing mitochondrial ROS, increasing mitochondrial membrane potential (MMP), and promoting the mRNA expression of genes associated with mitochondrial biogenesis (PGC-1α, TFAM, NRF1, and SIRT3) and mitochondrial fusion (MFN2, OPA1). Collectively, these findings demonstrate the protective effects of nanoceria against Ang II-mediated mitochondrial dysfunction and pathological hypertrophy in H9c2 cells.

SUBMITTER: Gul R

PROVIDER: S-EPMC10135342 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Protective Effects of Nanoceria against Mitochondrial Dysfunction and Angiotensin II-Induced Hypertrophy in H9c2 Cardiomyoblasts.

Gul Rukhsana R Dar Mushtaq A MA Nawaz Shahid S Alfadda Assim A AA

Antioxidants (Basel, Switzerland) 20230404 4

Mitochondrial dysfunction triggered by increased reactive oxygen species (ROS) generation is involved in the pathogenesis and development of cardiac hypertrophy. Nanoceria (cerium oxide nanoparticle) has powerful ROS-scavenging properties and is considered a potential therapeutic option for curbing ROS-related disorders. Here, we explored the signaling mechanism underlying the protective effects of nanoceria against angiotensin (Ang) II-stimulated pathological response in H9c2 cardiomyoblasts. O ...[more]

PMID: 37107252

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Project description:Hypertrophy of myocytes has been implicated in cardiac dysfunctions affecting wall stress and patterns of gene expression. However, molecular targets potentially preventing cardiac hypertrophy have not been fully elucidated. In the present study, we demonstrate that upregulation of catalase by peroxisome proliferator-activated receptor δ (PPARδ) is involved in the anti-hypertrophic activity of PPARδ in angiotensin II (Ang II)-treated H9c2 cardiomyocytes. Activation of PPARδ by a specific ligand GW501516 significantly inhibited Ang II-induced hypertrophy and the generation of reactive oxygen species (ROS) in H9c2 cardiomyocytes. These effects of GW501516 were almost completely abolished in cells stably expressing small hairpin (sh)RNA targeting PPARδ, indicating that PPARδ mediates these effects. Significant concentration and time-dependent increases in catalase at both mRNA and protein levels were observed in GW501516-treated H9c2 cardiomyocytes. In addition, GW501516-activated PPARδ significantly enhanced catalase promoter activity and protein expression, even in the presence of Ang II. GW501516-activated PPARδ also inhibited the expression of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), which are both marker proteins for hypertrophy. The effects of GW501516 on the expression of ANP and BNP were reversed by 3-amino-1,2,4-triazole (3-AT), a catalase inhibitor. Inhibition or downregulation of catalase by 3-AT or small interfering (si)RNA, respectively, abrogated the effects of PPARδ on Ang II-induced hypertrophy and ROS generation, indicating that these effects of PPARδ are mediated through catalase induction. Furthermore, GW501516-activated PPARδ exerted catalase-dependent inhibitory effects on Ang II-induced hypertrophy by blocking p38 mitogen-activated protein kinase. Taken together, these results indicate that the anti-hypertrophic activity of PPARδ may be achieved, at least in part, by sequestering ROS through fine-tuning the expression of catalase in cardiomyocytes.

Project description:This study investigates the differential cytotoxicity of reduced graphene oxide (RGO) and graphene oxide (GO) particles using an angiotensin II (Ang II)-induced hypertrophy model in H9c2 cells. Herein, GO particles were synthesized from graphite, and subsequent reduction was carried out to obtain RGO particles. To ensure a thorough assessment of particle size, functionalization, and purity, the particles were characterized by using UV-vis absorbance spectroscopy, dynamic light scattering, X-ray photoelectron spectroscopy, FTIR spectroscopy, Raman spectroscopy, and scanning electron microscopy. Comprehensive characterization revealed that the transformation from GO (∼21.6% content of oxygen) to RGO (∼13.3% content of oxygen) results in an enrichment in the proportion of sp2 carbon. Additionally, rat cardiac myoblasts of the H9c2 cell line were subjected to Ang II to induce cellular hypertrophy, leading to cytoskeleton remodeling, increased cardiac myocyte surface area, extracellular matrix alterations, and collagen type 1a upregulation. To evaluate cytotoxicity, H9c2 cells were treated with RGO and GO suspensions at concentrations ranging from 1 to 10,000 μg/mL, and metabolic viability was assessed in both concentration- and time-dependent assays. GO and RGO reduced the viability of H9c2 cells; however, the metabolic viability assays showed that the half-maximal inhibitory concentration (IC50) values for GO and RGO were significantly lower in hypertrophic cardiomyocytes, with GO exhibiting an IC50 of 12.6 ± 10.7 μg/mL and RGO exhibiting an IC50 of 86.3 ± 12.9 μg/mL, compared to control cells (676.0 ± 80.3 μg/mL for GO and 152.9 ± 40.1 μg/mL for RGO). These results demonstrate that under hypertrophic conditions, there is a significant increase of cytotoxicity for GO (50-fold increase) in comparison to RGO (1.7-fold increase). It was demonstrated that GO particles create a pro-oxidative environment that ultimately leads to mechanistic impairments and cell death. Vulnerable populations predisposed to cardiac damage may be at increased risk of experiencing toxicity caused by the use of GO particles in potential bioapplications.

Project description:BackgroundMitochondrial dysfunction would ultimately lead to myocardial cell apoptosis and death during ischemia-reperfusion injuries. Autophagy could ameliorate mitochondrial dysfunction by autophagosome forming, which is a catabolic process to preserve the mitochondrial's structural and functional integrity. HO-1 induction and expression are important protective mechanisms. This study in order to investigate the role of HO-1 during mitochondrial damage and its mechanism.Methods and resultsThe H9c2 cardiomyocyte cell line were incubated by hypoxic and then reoxygenated for the indicated time (2, 6, 12, 18, and 24 h). Cell viability was tested with CCK-8 kit. The expression of endogenous HO-1(RT-PCR and Western blot) increased with the duration of reoxygenation and reached maximum levels after 2 hours of H/R; thereafter, the expression gradually decreased to a stable level. Mitochondrial dysfunction (Flow cytometry quantified the ROS generation and JC-1 staining) and autophagy (The Confocal microscopy measured the autophagy. RFP-GFP-LC3 double-labeled adenovirus was used for testing.) were induced after 6 hours of H/R. Then, genetic engineering technology was employed to construct an Lv-HO1-H9c2 cell line. When HO-1 was overexpressed, the LC3II levels were significantly increased after reoxygenation, p62 protein expression was significantly decreased, the level of autophagy was unchanged, the mitochondrial membrane potential was significantly increased, and the mitochondrial ROS level was significantly decreased. Furthermore, when the HO-1 inhibitor ZnPP was applied the level of autophagy after reoxygenation was significantly inhibited, and no significant improvement in mitochondrial dysfunction was observed.ConclusionsDuring myocardial hypoxia-reoxygenation injury, HO-1 overexpression induces autophagy to protect the stability of the mitochondrial membrane and reduce the amount of mitochondrial oxidation products, thereby exerting a protective effect.

Dataset Information

Protective Effects of Nanoceria against Mitochondrial Dysfunction and Angiotensin II-Induced Hypertrophy in H9c2 Cardiomyoblasts.

Publications

Protective Effects of Nanoceria against Mitochondrial Dysfunction and Angiotensin II-Induced Hypertrophy in H9c2 Cardiomyoblasts.

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