p53 isoform Δ113p53 promotes zebrafish heart regeneration by maintaining redox homeostasis

Ye, Shengfan; Zhao, Ting; Zhang, Wei; Tang, Zimu; Gao, Ce; Ma, Zuwei; Xiong, Jing-Wei; Peng, Jinrong; Tan, Wei‐Qiang

doi:10.1038/s41419-020-02781-7

Cited by 14 publications

(22 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To explore whether Δ113p53 -positive radial glia cells contribute to the neuronal renewal process, a cell lineage tracing assay was performed. The tg(Δ113p53:CreER) transgenic zebrafish generated with a 3.6-kb fragment of the Δ113p53 promoter to drive CreER (tamoxifen-inducible Cre recombinase–estrogen receptor fusion protein) expression in our previous study was crossed with tg(β-act2:RSG) zebrafish to construct tg(Δ113p53:CreER ; β-act2:RSG) double-transgenic fish 23 . The tg(Δ113p53:GFP) zebrafish larvae were used to investigate if Δ113p53 expresses in radial glia cells at an early stage.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous studies have demonstrated that the expression of either human Δ133p53 or zebrafish Δ113p53 is upregulated by low levels of ROS signals in cell culture and zebrafish heart regeneration respectively. Both of Δ133p53 and Δ113p53 function to promote cell survival or proliferation by upregulating the expression of antioxidant genes 22 , 23 . Therefore, we investigated whether the expression of Δ113p53 is related to maintaining redox homeostasis in the zebrafish brain.…”

Section: Resultsmentioning

confidence: 99%

“…Oxidative stress has been proposed to trigger neurodegenerative diseases and accelerate aging 3 , 5 . Our previous studies have revealed that human Δ133p53 is highly induced in response to low levels of ROS and functions to promote cell survival by promoting the expression of antioxidant genes, whereas zebrafish Δ113p53 is induced by ROS signal during heart regeneration and promotes cardiomyocyte proliferation by maintaining redox homeostasis 22 , 23 . It has also been reported that human Δ133p53 expresses in astrocytes and prevents astrocytes from cell death and senescence.…”

Section: Discussionmentioning

confidence: 99%

“…In response to sub-toxic ROS stresses, Δ133p53 is also induced to promote cell survival and prevent senescence by coordinating with full-length p53 to transcribe antioxidant genes 22 . Our recent study revealed that zebrafish Δ113p53 is induced by heart injury to promote heart regeneration by maintaining redox homeostasis 23 . The basal expression of Δ133p53 prevents normal human fibroblasts, T lymphocytes, and astrocytes from replicative senescence by repressing p21 and miR-34a expression 24 – 26 .…”

Section: Introductionmentioning

confidence: 99%

“…Our previous studies have shown that Δ113p53 M/M mutant fish have normal development and growth though they are more sensitive to DNA damage stresses and have defects in heart regeneration 20 , 23 . Therefore, it is interesting to know in what kinds of zebrafish brain cells Δ113p53 expresses and if it plays a role in brain aging at the normal condition.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Loss-of-function of p53 isoform Δ113p53 accelerates brain aging in zebrafish

Zhao

Tang

et al. 2021

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

Reactive oxygen species (ROS) stress has been demonstrated as potentially critical for induction and maintenance of cellular senescence, and been considered as a contributing factor in aging and in various neurological disorders including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). In response to low-level ROS stress, the expression of Δ133p53, a human p53 isoform, is upregulated to promote cell survival and protect cells from senescence by enhancing the expression of antioxidant genes. In normal conditions, the basal expression of Δ133p53 prevents human fibroblasts, T lymphocytes, and astrocytes from replicative senescence. It has been also found that brain tissues from AD and ALS patients showed decreased Δ133p53 expression. However, it is uncharacterized if Δ133p53 plays a role in brain aging. Here, we report that zebrafish Δ113p53, an ortholog of human Δ133p53, mainly expressed in some of the radial glial cells along the telencephalon ventricular zone in a full-length p53-dependent manner. EDU-labeling and cell lineage tracing showed that Δ113p53-positive cells underwent cell proliferation to contribute to the neuron renewal process. Importantly, Δ113p53M/M mutant telencephalon possessed less proliferation cells and more senescent cells compared to wild-type (WT) zebrafish telencephalon since 9-months old, which was associated with decreased antioxidant genes expression and increased level of ROS in the mutant telencephalon. More interestingly, unlike the mutant fish at 5-months old with cognition ability, Δ113p53M/M zebrafish, but not WT zebrafish, lost their learning and memory ability at 19-months old. The results demonstrate that Δ113p53 protects the brain from aging by its antioxidant function. Our finding provides evidence at the organism level to show that depletion of Δ113p53/Δ133p53 may result in long-term ROS stress, and finally lead to age-related diseases, such as AD and ALS in humans.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Loss-of-function of p53 isoform Δ113p53 accelerates brain aging in zebrafish

Zhao

Tang

et al. 2021

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

show abstract

A novel gene-trap line reveals the dynamic patterns and essential roles of cysteine and glycine-rich protein 3 in zebrafish heart development and regeneration

Liang,

Zhou,

Chang

et al. 2024

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Mutations in cysteine and glycine-rich protein 3 (CSRP3)/muscle LIM protein (MLP), a key regulator of striated muscle function, have been linked to hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) in patients. However, the roles of CSRP3 in heart development and regeneration are not completely understood. In this study, we characterized a novel zebrafish gene-trap line, gSAIzGFFM218A, which harbors an insertion in the csrp3 genomic locus, heterozygous fish served as a csrp3 expression reporter line and homozygous fish served as a csrp3 mutant line. We discovered that csrp3 is specifically expressed in larval ventricular cardiomyocytes (CMs) and that csrp3 deficiency leads to excessive trabeculation, a common feature of CSRP3-related HCM and DCM. We further revealed that csrp3 expression increased in response to different cardiac injuries and was regulated by several signaling pathways vital for heart regeneration. Csrp3 deficiency impeded zebrafish heart regeneration by impairing CM dedifferentiation, hindering sarcomere reassembly, and reducing CM proliferation while aggravating apoptosis. Csrp3 overexpression promoted CM proliferation after injury and ameliorated the impairment of ventricle regeneration caused by pharmacological inhibition of multiple signaling pathways. Our study highlights the critical role of Csrp3 in both zebrafish heart development and regeneration, and provides a valuable animal model for further functional exploration that will shed light on the molecular pathogenesis of CSRP3-related human cardiac diseases.

show abstract

Identification and characterization of a novel upstream promoter of zebrafish p53 gene

Tian,

Zhu,

et al. 2024

Mol Biol Rep

View full text Add to dashboard Cite

p53 isoform Δ113p53 promotes zebrafish heart regeneration by maintaining redox homeostasis

Cited by 14 publications

References 68 publications

Loss-of-function of p53 isoform Δ113p53 accelerates brain aging in zebrafish

Loss-of-function of p53 isoform Δ113p53 accelerates brain aging in zebrafish

A novel gene-trap line reveals the dynamic patterns and essential roles of cysteine and glycine-rich protein 3 in zebrafish heart development and regeneration

Identification and characterization of a novel upstream promoter of zebrafish p53 gene

Contact Info

Product

Resources

About