H9c2 Cardiomyocytes under Hypoxic Stress: Biological Effects Mediated by Sentinel Downstream Targets

Boccellino, Mariarosaria; Galasso, Giovanni; Ambrosio, Pasqualina; Stiuso, Paola; Lama, Stefania; Zazzo, Erika Di; Schiavon, Sonia; Vecchio, Danièle; D’Ambrosio, Luca; Quagliuolo, Lucio; Feola, Antonia; Frati, Giacomo; Domenico, Marina Di

doi:10.1155/2021/6874146

Cited by 8 publications

(5 citation statements)

References 58 publications

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“…Moreover, desmin alterations elicited by various oxidants are partially but significantly attenuated in H9c2 cells transfected with desmin C333S. Indeed, as H9c2 cardiomyoblasts also express vimentin [ 78 , 79 ], a partial protective effect of mutant desmin could be foreseen since endogenous vimentin would still be susceptible to the effect of electrophiles, and could influence the impact of these compounds on the intermediate filament network. Nevertheless, the lower susceptibility of desmin C333S to oxidative stress-elicited network remodeling has also been evidenced in SW13/cl.2 cells, which do not express other cytoplasmic intermediate filaments, thus highlighting the role of this cysteine residue in network reorganization.…”

Section: Discussionmentioning

confidence: 99%

Desmin Reorganization by Stimuli Inducing Oxidative Stress and Electrophiles: Role of Its Single Cysteine Residue

Moneo-Corcuera,

Viedma-Poyatos,

Stamatakis

et al. 2023

Antioxidants

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The type III intermediate filament proteins vimentin and GFAP are modulated by oxidants and electrophiles, mainly through perturbation of their single cysteine residues. Desmin, the type III intermediate filament protein specific to muscle cells, is critical for muscle homeostasis, playing a key role in sarcomere organization and mitochondrial function. Here, we have studied the impact of oxidants and cysteine-reactive agents on desmin behavior. Our results show that several reactive species and drugs induce covalent modifications of desmin in vitro, of which its single cysteine residue, C333, is an important target. Moreover, stimuli eliciting oxidative stress or lipoxidation, including H2O2, 15-deoxy-prostaglandin J2, and CoCl2-elicited chemical hypoxia, provoke desmin disorganization in H9c2 rat cardiomyoblasts transfected with wild-type desmin, which is partially attenuated in cells expressing a C333S mutant. Notably, in cells lacking other cytoplasmic intermediate filaments, network formation by desmin C333S appears less efficient than that of desmin wt, especially when these proteins are expressed as fluorescent fusion constructs. Nevertheless, in these cells, the desmin C333S organization is also protected from disruption by oxidants. Taken together, our results indicate that desmin is a target for oxidative and electrophilic stress, which elicit desmin remodeling conditioned by the presence of its single cysteine residue.

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Section: Discussionmentioning

confidence: 99%

Desmin Reorganization by Stimuli Inducing Oxidative Stress and Electrophiles: Role of Its Single Cysteine Residue

Moneo-Corcuera,

Viedma-Poyatos,

Stamatakis

et al. 2023

Antioxidants

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“…The PC12 cells were treated with two concentrations of RSV (Sigma Aldrich, R5010, St. Louis, MO, USA) (2.5 and 10 µM in 0.05% DMSO in RPMI 1640 medium), and with an appropriate control for 24 h at 37 °C before hypoxic induction. For induction of the hypoxia model, after culture at 37 °C with 5% CO 2 for 24 h, the PC12 cells were placed in a hypoxic chamber (Billups-Rothenburg, Del Mar, CA, USA) and exposed to oxygen-deprived gas (1% O 2 , 5% CO 2 , 92% N 2 ) for 6 h, as reported [ 29 , 30 ]. The cells were then cultured under normal conditions for 24 h and harvested for further analysis.…”

Section: Methodsmentioning

confidence: 99%

Protective Effect of Resveratrol against Hypoxia-Induced Neural Oxidative Stress

Auti

Alessio

Ballini

et al. 2022

JPM

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Oxidative stress plays an important role in brain aging and in neurodegenerative diseases. New therapeutic agents are necessary to cross the blood–brain barrier and target disease pathogenesis without causing disagreeable side effects. Resveratrol (RSV) may act as a neuroprotective compound, but little is known about its potential in improving the cognitive and metabolic aspects that are associated with neurodegenerative diseases. The objective of this study was to investigate the protective effects and the underlying mechanisms of RSV against hypoxia-induced oxidative stress in neuronal PC12 cells. For the induction of the hypoxia model, the cells were exposed to oxygen-deprived gas in a hypoxic chamber. Cell cycle and apoptosis were analyzed by a fluorescence activated cell sorting (FACS) analysis. The intracellular reactive oxygen species (ROS) level was analyzed by using dichlorodihydrofluorescein diacetate (DCFDA) and 5-(and-6)-chloromethyl-2’,7’-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA) tests. The expression of activated caspase-3, -9, Bcl-2, Bax, p53, and SOD was investigated by a Western blot analysis. We found that hypoxia reduced PC12 viability by inducing apoptosis, while RSV treatment attenuated the ROS-induced damage by reducing caspase-3, -9, and the Bax/Bcl-2 ratio. The RSV treated groups were found to improve cellular health, with a 7.41% increase in the S phase population in the 10 µM group, compared to the control. Hence, RSV has a protective effect in neuronal cells and may halt the cell cycle in the G1/S phase to repair the intracellular damage. Therefore, RSV could be a good candidate to act as an antioxidant and promising preventive therapeutic agent in neurodegenerative diseases for personalized medicine.

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“…However, in the presence of hypoxia, ischemia, disease or ageing, NOS enzyme activity decreases, and endogenous NO production through the l -NOS pathway is reduced. Currently, the NO 3 − /NO 2 − /NO pathway activity is enhanced to maintain NO homeostasis [ 111 , 112 ]. NO participates in numerous physiological functions of the human body (such as regulation of cardiomyocyte function, nerve transmission function, platelet function, etc.…”

Section: Relationship Between Nrb and Their Metabolic Process And Hos...mentioning

confidence: 99%

From nitrate to NO: potential effects of nitrate-reducing bacteria on systemic health and disease

Liu,

Huang,

Huang

et al. 2023

Eur J Med Res

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Current research has described improving multisystem disease and organ function through dietary nitrate (DN) supplementation. They have provided some evidence that these floras with nitrate (NO3−) reductase are mediators of the underlying mechanism. Symbiotic bacteria with nitrate reductase activity (NRA) are found in the human digestive tract, including the mouth, esophagus and gastrointestinal tract (GT). Nitrate in food can be converted to nitrite under the tongue or in the stomach by these symbiotic bacteria. Then, nitrite is transformed to nitric oxide (NO) by non-enzymatic synthesis. NO is currently recognized as a potent bioactive agent with biological activities, such as vasodilation, regulation of cardiomyocyte function, neurotransmission, suppression of platelet agglutination, and prevention of vascular smooth muscle cell proliferation. NO also can be produced through the conventional l-arginine–NO synthase (l-NOS) pathway, whereas endogenous NO production by l-arginine is inhibited under hypoxia–ischemia or disease conditions. In contrast, exogenous NO3−/NO2−/NO activity is enhanced and becomes a practical supplemental pathway for NO in the body, playing an essential role in various physiological activities. Moreover, many diseases (such as metabolic or geriatric diseases) are primarily associated with disorders of endogenous NO synthesis, and NO generation from the exogenous NO3−/NO2−/NO route can partially alleviate the disease progression. The imbalance of NO in the body may be one of the potential mechanisms of disease development. Therefore, the impact of these floras with nitrate reductase on host systemic health through exogenous NO3−/NO2−/NO pathway production of NO or direct regulation of floras ecological balance is essential (e.g., regulation of body homeostasis, amelioration of diseases, etc.). This review summarizes the bacteria with nitrate reductase in humans, emphasizing the relationship between the metabolic processes of this microflora and host systemic health and disease. The potential effects of nitrate reduction bacteria on human health and disease were also highlighted in disease models from different human systems, including digestive, cardiovascular, endocrine, nervous, respiratory, and urinary systems, providing innovative ideas for future disease diagnosis and treatment based on nitrate reduction bacteria.

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H9c2 Cardiomyocytes under Hypoxic Stress: Biological Effects Mediated by Sentinel Downstream Targets

Cited by 8 publications

References 58 publications

Desmin Reorganization by Stimuli Inducing Oxidative Stress and Electrophiles: Role of Its Single Cysteine Residue

Desmin Reorganization by Stimuli Inducing Oxidative Stress and Electrophiles: Role of Its Single Cysteine Residue

Protective Effect of Resveratrol against Hypoxia-Induced Neural Oxidative Stress

From nitrate to NO: potential effects of nitrate-reducing bacteria on systemic health and disease

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