MS-based proteomic analysis of cardiac response to hypoxia in the goldfish (Carassius auratus)

Imbrogno, Sandra; Aiello, Donatella; Filice, Mariacristina; Leo, Serena; Mazza, Rosa; Cerra, Maria Carmela; Napoli, Anna

doi:10.1038/s41598-019-55497-w

Cited by 33 publications

(27 citation statements)

References 67 publications

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“…The remarkable ability of the goldfish heart to enhance its basal performance when exposed to a hypoxic milieu has been largely documented by studies from our laboratory [7,8,12]. These studies reported that in C. auratus, exposure to hypoxia is accompanied by an increased expression of cardiac HIF-1α (hypoxia-inducible factor 1α) and NOS.…”

Section: Pi3-k/akt/nos/no Pathway Activationmentioning

confidence: 99%

“…Thus, they represent valuable experimental models for studying the physiological strategies that allow animals to survive with reduced oxygen. In several fish species, the resistance to protracted hypoxia/anoxia is supported by a preserved cardiac activity and autonomic cardiovascular control [ 7 , 8 , 9 ]. This allows them not only to mobilize glucose from hepatic glycogen stores to all tissues, but also to transport lactate to the muscle, where it is converted into the less harmful ethanol, rapidly removed via the branchial epithelium [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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The Hypoxia Tolerance of the Goldfish (Carassius auratus) Heart: The NOS/NO System and Beyond

et al. 2020

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The extraordinary capacity of the goldfish (Carassius auratus) to increase its cardiac performance under acute hypoxia is crucial in ensuring adequate oxygen supply to tissues and organs. However, the underlying physiological mechanisms are not yet completely elucidated. By employing an ex vivo working heart preparation, we observed that the time-dependent enhancement of contractility, distinctive of the hypoxic goldfish heart, is abolished by the Nitric Oxide Synthase (NOS) antagonist L-NMMA, the Nitric Oxide (NO) scavenger PTIO, as well as by the PI3-kinase (PI3-K) and sarco/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) pumps’ inhibition by Wortmannin and Thapsigargin, respectively. In goldfish hearts exposed to hypoxia, an ELISA test revealed no changes in cGMP levels, while Western Blotting analysis showed an enhanced expression of the phosphorylated protein kinase B (pAkt) and of the NADPH oxidase catalytic subunit Nox2 (gp91phox). A significant decrease of protein S-nitrosylation was observed by Biotin Switch assay in hypoxic hearts. Results suggest a role for a PI3-K/Akt-mediated activation of the NOS-dependent NO production, and SERCA2a pumps in the mechanisms conferring benefits to the goldfish heart under hypoxia. They also propose protein denitrosylation, and the possibility of nitration, as parallel intracellular events.

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Section: Pi3-k/akt/nos/no Pathway Activationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Hypoxia Tolerance of the Goldfish (Carassius auratus) Heart: The NOS/NO System and Beyond

et al. 2020

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“…However, studies of the hypoxic responses of proteomes in other organs and tissues of fish remain limited. For example, in the heart of goldfish, hypoxia deregulated five enzymes involved in glycolysis and gluconeogenesis, including fructose-1,6-bisphosphate aldolase (Imbrogno et al, 2019). Presently, we attempted to elucidate the proteomic changes of fish brains after short-term and multi-generational hypoxia exposures.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Response of the Brain to Hypoxic Stress in Marine Medaka Fish (Oryzias melastigma)

et al. 2021

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Hypoxia is a serious issue that affects the marine environment, with a growing number of hypoxic “dead zones” occurring each year. Reports have indicated that hypoxia is detrimental to the reproductive function and sexual development of fish via the disruption of endocrine signaling in organs involved in the hypothalamus–pituitary–gonad axis, including the brain. While we previously reported that hypoxia induces transcriptome-wide alterations in the brain of marine medaka (Oryzias melastigma), whether these effects were reflected at the protein level remains unclear. Therefore, the present study used high-throughput proteomic sequencing along with bioinformatics analysis to assess the short-term and multi-generational effects of hypoxia on the brain proteome of O. melastigma. We identified 36,567 peptides and 7,599 proteins (1% false discovery rate in brain samples), with functions involved in cellular and metabolic processes such as signaling and reproductive processes as well as energy production and conversion. Furthermore, we determined that hypoxia resulted in the significant differential expressions of 33 upregulated and 69 downregulated proteins in the short-term exposure group and 24 upregulated and 52 downregulated proteins in the multi-generational exposure group. Pathway enrichment analysis of the deregulated proteins indicated that hypoxia could impair brain function by altering arachidonic acid metabolism, tight junctions, and adrenergic signaling under short-term hypoxic exposure and by altering p53 and PI3K–Akt signaling under multi-generational hypoxic exposure, which may lead to the onset of neurodegenerative disorders including Alzheimer’s disease and amyotrophic lateral sclerosis. Ingenuity pathway analysis of the deregulated proteins showed that hypoxia affected common signaling pathways in the brain (e.g., integrin, paxillin, and epithelial adherens junction signaling) under both short-term and multi-generational exposures. Hypoxia also deregulated pathways specific to short-term exposure (including integrin-linked kinase, calcium, and integrin signaling) and multi-generational exposure (including sphingosine-1-phosphate signaling, endocannabinoid neuronal synapse pathway, and endoplasmic reticulum stress pathway). Overall, our results provide additional insights into the mechanisms of hypoxia disrupting neuronal function at the protein level in marine medaka.

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“…This suggests that the enhancement of myocardial contractility observed in the goldfish in response to low O 2 is associated with a low accumulation of cardiac lactate. In addition, authors reported a parallel slight reduction in pyruvate levels (Imbrogno et al 2019a): this implies the activation of alternative metabolic pathways (e.g., gluconeogenesis) which, by allowing a reutilization of the first product of the anaerobic glycolysis, enhance anaerobic ATP yield and minimize metabolic acidosis. Mass spectrometry-based proteomic analysis led to the identification of two isoforms of fructose-bisphosphate aldolase differently expressed in homogenates of goldfish heart exposed to normoxic or hypoxic medium (Imbrogno et al 2019a).…”

Section: Hypoxiamentioning

confidence: 99%

“…In addition, authors reported a parallel slight reduction in pyruvate levels (Imbrogno et al 2019a): this implies the activation of alternative metabolic pathways (e.g., gluconeogenesis) which, by allowing a reutilization of the first product of the anaerobic glycolysis, enhance anaerobic ATP yield and minimize metabolic acidosis. Mass spectrometry-based proteomic analysis led to the identification of two isoforms of fructose-bisphosphate aldolase differently expressed in homogenates of goldfish heart exposed to normoxic or hypoxic medium (Imbrogno et al 2019a). Particularly, Aldolase C, mainly effective in glycolysis (Penhoet et al 1969;Penhoet and Rutter 1971), has been found in the normoxic heart, while aldolase B, which has evolved to have a role in gluconeogenesis (Penhoet and Rutter 1971;Penhoet et al 1969), has been mainly revealed in the hypoxic counterpart (Imbrogno et al 2019a).…”

Section: Hypoxiamentioning

confidence: 99%

The goldfish Carassius auratus: an emerging animal model for comparative cardiac research

2021

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The use of unconventional model organisms is significantly increasing in different fields of research, widely contributing to advance life sciences understanding. Among fishes, the cyprinid Carassius auratus (goldfish) is largely used for studies on comparative and evolutionary endocrinology, neurobiology, adaptive and conservation physiology, as well as for translational research aimed to explore mechanisms that may be useful in an applicative biomedical context. More recently, the research possibilities offered by the goldfish are further expanded to cardiac studies. A growing literature is available to illustrate the complex networks involved in the modulation of the goldfish cardiac performance, also in relation to the influence of environmental signals. However, an overview on the existing current knowledge is not yet available. By discussing the mechanisms that in C. auratus finely regulate the cardiac function under basal conditions and under environmental challenges, this review highlights the remarkable flexibility of the goldfish heart in relation not only to the basic morpho-functional design and complex neuro-humoral traits, but also to its extraordinary biochemical-metabolic plasticity and its adaptive potential. The purpose of this review is also to emphasize the power of the heart of C. auratus as an experimental tool useful to investigate mechanisms that could be difficult to explore using more conventional animal models and complex cardiac designs.

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MS-based proteomic analysis of cardiac response to hypoxia in the goldfish (Carassius auratus)

Cited by 33 publications

References 67 publications

The Hypoxia Tolerance of the Goldfish (Carassius auratus) Heart: The NOS/NO System and Beyond

The Hypoxia Tolerance of the Goldfish (Carassius auratus) Heart: The NOS/NO System and Beyond

Proteomic Response of the Brain to Hypoxic Stress in Marine Medaka Fish (Oryzias melastigma)

The goldfish Carassius auratus: an emerging animal model for comparative cardiac research

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