Modulation of the Isoprenoid/Cholesterol Biosynthetic Pathway During Neuronal Differentiation In Vitro

Cartocci, Veronica; Segatto, Marco; Tunno, Ilenia Di; Leone, Stefano; Pfrieger, Frank W.; Pallottini, Valentina

doi:10.1002/jcb.25500

Cited by 28 publications

(29 citation statements)

References 51 publications

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“…Given the role of cholesterol in the RBC membrane, it is plausible that cholesterol regulates cell survival. However, the function of the CSP might not be limited to cell death or stress mechanisms because previously published work has indicated a regulatory function for cholesterol and its derivatives at the level of cellular differentiation [53][54][55][56][57][58][59][60] . Future work that analyzes both primitive and definitive hematopoiesis at unique stages of differentiation in different model systems is likely to identify the exact cellular mechanisms underlying the phenotypic alteration we describe.…”

Section: Discussionmentioning

confidence: 99%

Mutations in the zebrafishhmgcs1gene reveal a novel function for isoprenoids during red blood cell development

Hernández

Castro

Reyes-Nava

et al. 2018

Preprint

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word count: 187 Number of figures and tables: 5 Number of references: 72 Key Points 1. The products of the cholesterol synthesis pathway regulate red blood cell development during primitive erythropoiesis. 2. Isoprenoids regulate erythropoiesis by modulating the expression of the GATA1 transcription factor. AbstractErythropoiesis is the process by which new red blood cells (RBCs) are formed and defects in this process can lead to anemia or thalassemia. The GATA1 transcription factor is an established mediator of RBC development. However, the upstream mechanisms that regulate the expression of GATA1 are not completely characterized. Cholesterol is one potential upstream mediator of GATA1 expression because previously published studies suggest that defects in cholesterol synthesis disrupt RBC differentiation. Here we characterize RBC development in a zebrafish harboring a single missense mutation in the hmgcs1 gene (Vu57 allele). hmgcs1 encodes the first enzyme in the cholesterol synthesis pathway and mutation of hmgcs1 inhibits cholesterol synthesis. We analyzed the number of RBCs in hmgcs1 mutants and their wildtype siblings. Mutation of hmgcs1 resulted in a decrease in the number of mature RBCs, which coincides with reduced gata1a expression. We combined these experiments with pharmacological inhibition and confirmed that cholesterol and isoprenoid synthesis are essential for RBC differentiation, but that gata1a expression is isoprenoid dependent. Collectively, our results reveal two novel upstream regulators of RBC development and suggest that appropriate cholesterol homeostasis is critical for primitive erythropoiesis.

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Section: Discussionmentioning

confidence: 99%

Mutations in the zebrafishhmgcs1gene reveal a novel function for isoprenoids during red blood cell development

Hernández

Castro

Reyes-Nava

et al. 2018

Preprint

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“…Intriguingly, the modulation of the activity of specific prenylated proteins, Rab3, and RhoA, which share with cholesterol the same biosynthetic pathway are involved in neurotransmitter release and synaptic plasticity, respectively (Segatto et al, ). Moreover, RhoA is also involved in neurite outgrowth, so could be implicated in neurodevelopmental pathologies (Cartocci et al, ).…”

Section: Discussionmentioning

confidence: 99%

Can Cholesterol Metabolism Modulation Affect Brain Function and Behavior?

Cartocci

Servadio

Trezza

et al. 2016

Journal Cellular Physiology

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Cholesterol is an important component for cell physiology. It regulates the fluidity of cell membranes and determines the physical and biochemical properties of proteins. In the central nervous system, cholesterol controls synapse formation and function and supports the saltatory conduction of action potential. In recent years, the role of cholesterol in the brain has caught the attention of several research groups since a breakdown of cholesterol metabolism has been associated with different neurodevelopmental and neurodegenerative diseases, and interestingly also with psychiatric conditions. The aim of this review is to summarize the current knowledge about the connection between cholesterol dysregulation and various neurologic and psychiatric disorders based on clinical and preclinical studies. J. Cell. Physiol. 232: 281-286, 2017. © 2016 Wiley Periodicals, Inc.

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“…Cultured cells and TA muscles from WT and mdx mice were lysed in sample buffer (0.125 M Tris-HCl containing 10% SDS, protease inhibitor cocktail, pH 6.8) by sonication (duty cycle 20%, output 3) as previously described [ 23 , 24 ]. Subsequently, after the addition of the Laemmli buffer and denaturation at 95 °C for 5 min, the samples (twenty micrograms of proteins) were resolved on SDS-PAGE [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

ProNGF/p75NTR Axis Drives Fiber Type Specification by Inducing the Fast-Glycolytic Phenotype in Mouse Skeletal Muscle Cells

Pallottini

Colardo

Tonini

et al. 2020

Cells

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Despite its undisputable role in the homeostatic regulation of the nervous system, the nerve growth factor (NGF) also governs the relevant cellular processes in other tissues and organs. In this study, we aimed at assessing the expression and the putative involvement of NGF signaling in skeletal muscle physiology. To reach this objective, we employed satellite cell-derived myoblasts as an in vitro culture model. In vivo experiments were performed on Tibialis anterior from wild-type mice and an mdx mouse model of Duchenne muscular dystrophy. Targets of interest were mainly assessed by means of morphological, Western blot and qRT-PCR analysis. The results show that proNGF is involved in myogenic differentiation. Importantly, the proNGF/p75NTR pathway orchestrates a slow-to-fast fiber type transition by counteracting the expression of slow myosin heavy chain and that of oxidative markers. Concurrently, proNGF/p75NTR activation facilitates the induction of fast myosin heavy chain and of fast/glycolytic markers. Furthermore, we also provided evidence that the oxidative metabolism is impaired in mdx mice, and that these alterations are paralleled by a prominent buildup of proNGF and p75NTR. These findings underline that the proNGF/p75NTR pathway may play a crucial role in fiber type determination and suggest its prospective modulation as an innovative therapeutic approach to counteract muscle disorders.

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Modulation of the Isoprenoid/Cholesterol Biosynthetic Pathway During Neuronal Differentiation In Vitro

Cited by 28 publications

References 51 publications

Mutations in the zebrafishhmgcs1gene reveal a novel function for isoprenoids during red blood cell development

Mutations in the zebrafishhmgcs1gene reveal a novel function for isoprenoids during red blood cell development

Can Cholesterol Metabolism Modulation Affect Brain Function and Behavior?

ProNGF/p75NTR Axis Drives Fiber Type Specification by Inducing the Fast-Glycolytic Phenotype in Mouse Skeletal Muscle Cells

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