Control of Programmed Cell Death During Zebrafish Embryonic Development

Popgeorgiev, Nikolay; Bonneau, Benjamin; Prudent, Julien; Gillet, Germain

doi:10.5772/intechopen.74494

Cited by 5 publications

(4 citation statements)

References 93 publications

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“…Peripheral effects of cacna1aa LOF (2.5 ng + 2.5 ng) were evidenced by changes in morphology of morphants, i.e., slight hyperpigmentation, lack of swim bladder, and shorter body length-phenotypes also observed in other zebrafish models of epilepsy [22,40]. Notably, cacna1aa mRNA in zebrafish embryos is maternally contributed [41,42], possibly accounting for the higher mortality rate at 24 h than 4 h after injection. Saito et al [43] revealed that knockdown of Cacna1a to 28% of baseline Ca v 2.1 induced severe ataxia, while reduction to 14% dramatically shortened the lifespan of mice.…”

Section: Discussionmentioning

confidence: 89%

Phenotypic Characterization of Larval Zebrafish (Danio rerio) with Partial Knockdown of the cacna1a Gene

et al. 2019

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The CACNA1A gene encodes the pore-forming α1 subunit of voltage-gated P/Q type Ca 2+ channels (Ca v 2.1). Mutations in this gene, among others, have been described in patients and rodents suffering from absence seizures and episodic ataxia type 2 with/ without concomitant seizures. In this study, we aimed for the first time to assess phenotypic and behavioral alterations in larval zebrafish with partial cacna1aa knockdown, placing special emphasis on changes in epileptiform-like electrographic discharges in larval brains. Whole-mount in situ hybridization analysis revealed expression of cacna1aa in the optic tectum and medulla oblongata of larval zebrafish at 4 and 5 days post-fertilization. Next, microinjection of two antisense morpholino oligomers (individually or in combination) targeting all splice variants of cacna1aa into fertilized zebrafish eggs resulted in dose-dependent mortality and decreased or absent touch response. Over 90% knockdown of cacna1aa on protein level induced epileptiform-like discharges in the optic tectum of larval zebrafish brains. Incubation of morphants with antiseizure drugs (sodium valproate, ethosuximide, lamotrigine, topiramate) significantly decreased the number and, in some cases, cumulative duration of epileptiform-like discharges. In this context, sodium valproate seemed to be the least effective. Carbamazepine did not affect the number and duration of epileptiform-like discharges. Altogether, our data indicate that cacna1aa loss-of-function zebrafish may be considered a new model of absence epilepsy and may prove useful both for the investigation of Cacna1a-mediated epileptogenesis and for in vivo drug screening.

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Section: Discussionmentioning

confidence: 89%

Phenotypic Characterization of Larval Zebrafish (Danio rerio) with Partial Knockdown of the cacna1a Gene

et al. 2019

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“…Apoptosis is a self-destruction complex and a biochemical process of cells in a multicellular organism. A programmed cell death maintains tissue homeostasis, fetal development, and aging [3]. During apoptosis, the surrounding cells and cellular macromolecules are digested into smaller fragments.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, In vitro Antiproliferative and Cytotoxic Effect of Ruthenium(II)-Bipyridine-Benzoylpicolinic Acid Complex on SK-MEL-28 and Normal L6 Cell Lines

Sivaraman¹,

Daniel²

2022

Trends Sci

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The most seriously spread malignant tumor of melanocytes throughout the body is a melanoma type of skin cancer. SK-MEL-28 cell line is one of a series of melanoma cell lines. The objective of the present investigation is to study the anticancer activity and cytotoxicity of novel [Ru(bpy)2(bzpic)2]2+ (bpy = 2,2ʹ-bipyridine and bzpic = 3-Benzoylpicolinic acid) complex on SK-MEL-28 and normal L6 cell lines using MTT assay method. The morphology of the cancerous SK-MEL-28 cell line at various concentrations of the [Ru(bpy)2(bzpic)2]2+ complex is assessed by 2-fold dilution method, and the in vitro antiproliferative effect of the complex on the cancerous SK-MEL-28 cell line is analyzed by direct microscopic observation method. The percentage viability of the complex on cancerous SK-MEL-28 cell line at various concentrations is determined. The IC50 value of the complex against the SK-MEL-28 cell is found to be 39.109 µg/mL which shows good antiproliferative effect. The IC50 value of the complex against normal L6 cell line is found to be 55.315 µg/mL. The results revealed that the percentage of growth inhibition of the cell is based on dose-dependent manner and the formation of formazan crystal indicates this. The fluorescent microscopy observation clearly determines that the synthesized [Ru(bpy)2(bzpic)2]2+ complex shows late apoptosis on SK-MEL-28 cell line and early apoptosis on L6 cell line. Hence, it is evident that the synthesized complex exhibits good in vitro antiproliferative effect with lower cytotoxicity. HIGHLIGHTS Synthesis of [Ru(bpy)2(bzpic)2]2+ complex Direct and fluorescent microscopic observation of [Ru(bpy)2(bzpic)2]2+ complex on SK-MEL-28 and normal L6 cell lines In vitro antiproliferative and cytotoxic effects of [Ru(bpy)2(bzpic)2]2+ complex on SK-MEL-28 and normal L6 cell lines GRAPHICAL ABSTRACT

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“…The Bcl-2 family of proteins plays a major role in the regulation of apoptosis, a highly conserved programmed cell death process that eliminates unwanted cells, including damaged cells, which is essential during development [ 1 ]. Dysregulation of this process can lead to cancer or degenerative diseases [ 2 , 3 ] and multiple clinical trials aim to inhibit the Bcl-2 family proteins in cancer [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…There is evidence that impaired Bcl-x activity is correlated with the onset of major diseases such as Parkinson’s disease (PD) [ 11 , 12 ], amyotrophic lateral sclerosis [ 13 ] spinal cord muscular atrophy [ 14 ], as well as Friedrich ataxia [ 15 ], however the underlying molecular mechanisms remain poorly characterized. Actually, Bcl-xL seems to play critical roles in a large number of nerve cells, including astrocytes [ 13 ], neurons of the cortex [ 16 ], the hippocampus [ 10 ], the midbrain [ 17 ], the visual and the auditory systems [ 18 , 19 ], motoneurons (MN) [ 14 ] and sensory neurons of the dorsal root ganglion [ 1 ]. The bclx gene encodes 5 isoforms, including Bcl-xL, the major isoform in the CNS.…”

Section: Introductionmentioning

confidence: 99%

Involvement of Bcl-xL in Neuronal Function and Development

Bas

Nguyen

Gillet

2021

IJMS

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The B-cell lymphoma (Bcl-2) family of proteins are mainly known for their role in the regulation of apoptosis by preventing pore formation at the mitochondrial outer membrane and subsequent caspase activation. However, Bcl-2 proteins also have non-canonical functions, independent of apoptosis. Indeed, the cell death machinery, including Bcl-2 homologs, was reported to be essential for the central nervous system (CNS), notably with respect to synaptic transmission and axon pruning. Here we focused on Bcl-xL, a close Bcl-2 homolog, which plays a major role in neuronal development, as bclx knock out mice prematurely die at embryonic day 13.5, showing massive apoptosis in the CNS. In addition, we present evidence that Bcl-xL fosters ATP generation by the mitochondria to fuel high energy needs by neurons, and its contribution to synaptic transmission. We discuss how Bcl-xL might control local and transient activation of caspases in neurons without causing cell death. Consistently, Bcl-xL may contribute to morphological changes, such as sprouting and retractation of axon branches, in the context of CNS plasticity. Regarding degenerative diseases and aging, a better understanding of the numerous roles of the cell death machinery in neurons may have future clinical implications.

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Control of Programmed Cell Death During Zebrafish Embryonic Development

Cited by 5 publications

References 93 publications

Phenotypic Characterization of Larval Zebrafish (Danio rerio) with Partial Knockdown of the cacna1a Gene

Phenotypic Characterization of Larval Zebrafish (Danio rerio) with Partial Knockdown of the cacna1a Gene

Synthesis, Characterization, In vitro Antiproliferative and Cytotoxic Effect of Ruthenium(II)-Bipyridine-Benzoylpicolinic Acid Complex on SK-MEL-28 and Normal L6 Cell Lines

Involvement of Bcl-xL in Neuronal Function and Development

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