Topics

Histone deacetylase 6 inhibition restores autophagic flux to promote functional recovery after spinal cord injury.

07:00 EST 30th November 2019 | BioPortfolio

Summary of "Histone deacetylase 6 inhibition restores autophagic flux to promote functional recovery after spinal cord injury."

After spinal cord injury (SCI), the inhibitory molecules derived from scars at the lesion sites and the limited regenerative capacity of neuronal axons pose difficulties for the recovery after SCI. Remodeling of cytoskeleton structures including microtubule assembly and tubulin post-translational modification are widely accepted to play a crucial role in initiation of growth cone and regrowth of injured axon. Although increasing studies have focused on the association between tubulin acetylation and autophagy due to the role of tubulin acetylation in organelles and substances transport, there are no studies exploring the effect of tubulin acetylation on autophagy after spinal cord injury (SCI). Here, we found that histone deacetylase 6 (HDAC6) was significantly up-regulated after SCI, while inhibition of HDAC6 by Tubastatin A induced functional recovery after SCI. In view of enzyme-dependent and -independent mechanisms of HDAC6 to adjust diverse cellular processes, such as autophagy, the ubiquitin proteasome system and post-translational modification of tubulin, we mainly focused on the significance of HDAC6 in axonal regeneration and autophagy after SCI. Western blotting, Co-immunoprecipitation and immunofluorescence staining were conducted to showed that Tubastatin A treatment in nocodazole-treated cells and mice suffering from SCI prompted acetylation and stabilization of microtubules and thus restored transport function, which may contribute to restored autophagic flux and increased axonal length. Whereas inhibition of degradation of autolysosomes by bafilomycin A1 (Baf-A1) reversed functional recovery caused by Tubastatin A, revealing the association between tubulin acetylation and autophagy, which supports HDAC6 inhibition as a potential target for SCI treatment.

Affiliation

Journal Details

This article was published in the following journal.

Name: Experimental neurology
ISSN: 1090-2430
Pages: 113138

Links

DeepDyve research library

PubMed Articles [14904 Associated PubMed Articles listed on BioPortfolio]

Novel Benzohydroxamate-based Potent and Selective Histone Deacetylase 6 (HDAC6) Inhibitors Bearing a Pentaheterocyclic Scaffold: Design, Synthesis and Biological Evaluation.

Histone deacetylase 6 (HDAC6) is a peculiar HDAC isoform whose expression and functional alterations have been correlated with a variety of pathologies such as autoimmune disorders, neurodegenerative ...

Dipyridamole impairs autophagic flux and exerts antiproliferative activity on prostate cancer cells.

Autophagy is a cellular bulk degradation process used as an alternative source of energy and metabolites and implicated in various diseases. Inefficient autophagy in nutrient-deprived cancer cells wou...

Calpain regulates CVB3 induced viral myocarditis by promoting autophagic flux upon infection.

Calpains are calcium-activated neutral cysteine proteases. The dysregulation of calpain activity has been found to be related to cardiovascular diseases, for which calpain inhibition is used as a trea...

Histone Deacetylase 7 Inhibition in A Murine Model of Gram-Negative Pneumonia-Induced Acute Lung Injury.

Pulmonary infections remain the most common cause of Acute Respiratory Distress Syndrome (ARDS), a pulmonary inflammatory disease with high mortality, for which no targeted therapy currently exists. W...

Maduramicin inactivation of Akt impairs autophagic flux leading to accumulated autophagosomes-dependent apoptosis in skeletal myoblast cells.

It has been clinically documented that maduramicin (Mad), a polyether ionophore antibiotic widely used in the control of coccidiosis in poultry worldwide, can elicit skeletal muscle degeneration, hear...

Clinical Trials [5634 Associated Clinical Trials listed on BioPortfolio]

Imaging Histone Deacetylase in the Heart

The overall goal of this PET-MR imaging trial is to evaluate 11C-Martinostat, a histone deacetylase targeted radioligand, in patients with aortic stenosis, individuals with diabetes, and h...

Study of Vorinostat Plus Capecitabine (X) and Cisplatin (P) for 1st Line Treatment of Metastatic or Recurrent Gastric Cancer

There is scientific rationale for exploring the role of vorinostat, histone deacetylase inhibitor with capecitabine (X) and cisplatin (P), one of standard chemotherapy in patients with adv...

An Investigational Study of a Histone Deacetylase (HDAC) Inhibitor Plus Targretin in Cutaneous T-Cell Lymphoma Patients (0683-016)(TERMINATED)

This is an investigational study that increases the dosage to determine the safety/tolerability, and efficacy of a histone deacetylase inhibitor in combination with Targretin in patients w...

Tinostamustine and Nivolumab in Advanced Melanoma

This trial is a first-in-human drug combination with the first-in-class alkylating histone deacetylase inhibition (HDACi) fusion molecule Tinostamustine (EDO-S101) and the anti-PD-1 monocl...

Effect of Symbicort on HAT and HDAC in Sputum Macrophages of COPD

The purpose of the study is to compare histone acetyltransferase (HAT) and histone deacetylase (HDAC) expressions and activities in induced sputum macrophages obtained from patients with m...

Medical and Biotech [MESH] Definitions

A histone deacetylase subtype that is found along with HISTONE DEACETYLASE 2; RETINOBLASTOMA-BINDING PROTEIN 4; and RETINOBLASTOMA-BINDING PROTEIN 7 as core components of histone deacetylase complexes.

A histone deacetylase subtype that is found along with HISTONE DEACETYLASE 1; RETINOBLASTOMA-BINDING PROTEIN 4; and RETINOBLASTOMA-BINDING PROTEIN 7 as core components of histone deacetylase complexes.

A class II histone deacetylase that removes acetyl groups from N-terminal LYSINES of HISTONE H2A; HISTONE H2B; HISTONE H3; and HISTONE H4. It plays a critical role in EPIGENETIC REPRESSION and regulation of GENETIC TRANSCRIPTION, as well as CELL MOTILITY through deacetylation of TUBULIN. It also targets misfolded proteins for clearance by AUTOPHAGY when MOLECULAR CHAPERONE-mediated folding is overwhelmed.

A multisubunit enzyme complex that regulates GENETIC TRANSCRIPTION by deacetylating the HISTONE residues of NUCLEOSOMES.

A enzyme complex involved in the remodeling of NUCLEOSOMES. The complex is comprised of at least seven subunits and includes both histone deacetylase and ATPase activities.

Quick Search


DeepDyve research library

Relevant Topics

Spinal Cord Disorders
The spinal cord is a bundle of nerves that runs down the middle of the back which carry signals back and forth between the body and brain. It is protected by vertebrae, which are the bone disks that make up the spine. An accident that damages the verte...

Enzymes
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...


Searches Linking to this Article