Regulation of Neuronal Survival and Axon Growth by a Perinuclear cAMP Compartment

Boczek, Tomasz; Cameron, Evan G.; Yu, Wendou; Xia, Xin; Shah, Shweta; Chabeco, Boris Castillo; Galvão, Joana; Nahmou, Michael; Li, Jinliang; Thakur, Hrishikesh; Goldberg, Jeffrey L.; Kapiloff, Michael S.

doi:10.1523/jneurosci.2752-18.2019

Cited by 49 publications

(53 citation statements)

References 48 publications

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“…According to KEGG, the cAMP pathway is integral to the “Neuroactive ligand–receptor interaction” pathway ( Figure S1, File S4 ). cAMP plays a pivotal role in neuronal survival [ 25 ]. Thus, in this study, the concomitant induction of “cAMP signaling pathway” and the “Neuroactive ligand–receptor interaction” could indicate an increase in sensitivity of innervations in liver and mammary tissues in CS vs. MF pathway.…”

Section: Resultsmentioning

confidence: 99%

Diet Composition Affects Liver and Mammary Tissue Transcriptome in Primiparous Holstein Dairy Cows

Gao

Zhou

Wang

et al. 2020

Animals

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The objective of the present study was to evaluate the overall adaptations of liver and mammary tissue to a corn stover (CS) compared to a mixed forage (MF) diet in mid-lactation primiparous dairy cows. Twenty-four primiparous lactating Holstein cows were randomly allocated to 2 groups receiving either an alfalfa forage diet (MF, F:C = 60:40) with Chinese wildrye, alfalfa hay and corn silage as forage source or a corn stover forage diet (CS, F:C = 40:60). A subgroup of cows (n = 5/diet) was used for analysis of liver and mammary transcriptome using a 4 × 44K Bovine Agilent microarray chip. The results of functional annotation analysis showed that in liver CS vs. MF inhibited pathways related to lipid metabolism while induced the activity of the potassium channel. In mammary tissue, fatty acid metabolism was activated in CS vs. MF. In conclusion, the analysis of genes affected by CS vs. MF indicated mammary gland responding to lower level of linoleate from the diet (lower in CS vs. MF) by activating the associated biosynthesis metabolic pathway while the liver adaptively activated potassium transport to compensate for a lower K ingestion.

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Section: Resultsmentioning

confidence: 99%

Diet Composition Affects Liver and Mammary Tissue Transcriptome in Primiparous Holstein Dairy Cows

Gao

Zhou

Wang

et al. 2020

Animals

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“…Cell counting was performed as previously described [ 24 ]. In brief, retinas were divided into 4 quadrants.…”

Section: Methodsmentioning

confidence: 99%

MEF2 transcription factors differentially contribute to retinal ganglion cell loss after optic nerve injury

Xia¹,

Yu²,

Bian³

et al. 2020

PLoS ONE

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Loss of retinal ganglion cells (RGCs) in optic neuropathies results in permanent partial or complete blindness. Myocyte enhancer factor 2 (MEF2) transcription factors have been shown to play a pivotal role in neuronal systems, and in particular MEF2A knockout was shown to enhance RGC survival after optic nerve crush injury. Here we expanded these prior data to study bi-allelic, tri-allelic and heterozygous allele deletion. We observed that deletion of all MEF2A, MEF2C, and MEF2D alleles had no effect on RGC survival during development. Our extended experiments suggest that the majority of the neuroprotective effect was conferred by complete deletion of MEF2A but that MEF2D knockout, although not sufficient to increase RGC survival on its own, increased the positive effect of MEF2A knockout. Conversely, MEF2A over-expression in wildtype mice worsened RGC survival after optic nerve crush. Interestingly, MEF2 transcription factors are regulated by post-translational modification, including by calcineurin-catalyzed dephosphorylation of MEF2A Ser-408 known to increase MEF2A-dependent transactivation in neurons. However, neither phospho-mimetic nor phospho-ablative mutation of MEF2A Ser-408 affected the ability of MEF2A to promote RGC death in vivo after optic nerve injury. Together these findings demonstrate that MEF2 gene expression opposes RGC survival following axon injury in a complex hierarchy, and further support the hypothesis that loss of or interference with MEF2A expression might be beneficial for RGC neuroprotection in diseases such as glaucoma and other optic neuropathies.

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“…Notably, this latter strategy has been deployed outside the cardiovascular system. For example, expression of the 4D3 N-terminal peptide has been used to disrupt mAKAPα-PDE4D3complexes in the retinal ganglion cell to confer neuroprotection (Boczek et al, 2019).…”

Section: Future Perspectivesmentioning

confidence: 99%

Visualizing Cyclic Adenosine Monophosphate in Cardiac Microdomains Involved in Ion Homeostasis

2019

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3′,5′-Cyclic adenosine monophosphate (cAMP) is a key second messenger that regulates function of proteins involved in ion homeostasis and cardiac excitation-contraction coupling. Over the last decade, it has been increasingly appreciated that cAMP conveys its numerous effects by acting in discrete subcellular compartments or “microdomains.” In this mini review, we describe how such localized signals can be visualized in living cardiomyocytes to better understand cardiac physiology and disease. Special focus is made on targeted biosensors that can be used to resolve second messenger signals within nanometers of cardiac ion channels and transporters. Potential directions for future research and the translational importance of cAMP compartmentalization are discussed.

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Regulation of Neuronal Survival and Axon Growth by a Perinuclear cAMP Compartment

Cited by 49 publications

References 48 publications

Diet Composition Affects Liver and Mammary Tissue Transcriptome in Primiparous Holstein Dairy Cows

Diet Composition Affects Liver and Mammary Tissue Transcriptome in Primiparous Holstein Dairy Cows

MEF2 transcription factors differentially contribute to retinal ganglion cell loss after optic nerve injury

Visualizing Cyclic Adenosine Monophosphate in Cardiac Microdomains Involved in Ion Homeostasis

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