Class I HDACs control a JIP1-dependent pathway for kinesin-microtubule binding in cardiomyocytes

Blakeslee, Weston W.; Lin, Ying-Hsi; Stratton, Matthew S.; Tatman, Philip D.; Hu, Tianjing; Ferguson, Bradley S.; McKinsey, Timothy A.

doi:10.1016/j.yjmcc.2017.09.002

Cited by 12 publications

(6 citation statements)

References 43 publications

(49 reference statements)

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“…As discussed above, HDAC inhibitors are efficacious in pre-clinical animal models of HF [6,7,8,11,14,23,43,49]. However, molecular underpinnings for HDAC inhibitors in the heart have largely focused on their role in the regulation of histone (de)acetylation and gene expression [47,93]. Recent reports, however, have shown that HDAC inhibitors can target cytosolic and sarcomere proteins to improve cardiac function via improvements in muscle contractility [7], relaxation [14], autophagy [11], and proteotoxicity [8].…”

Section: Hdac Inhibition Protein Phosphorylation and Heart Failurementioning

confidence: 99%

The Crosstalk between Acetylation and Phosphorylation: Emerging New Roles for HDAC Inhibitors in the Heart

Habibian

Ferguson

2018

IJMS

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Approximately five million United States (U.S.) adults are diagnosed with heart failure (HF), with eight million U.S. adults projected to suffer from HF by 2030. With five-year mortality rates following HF diagnosis approximating 50%, novel therapeutic treatments are needed for HF patients. Pre-clinical animal models of HF have highlighted histone deacetylase (HDAC) inhibitors as efficacious therapeutics that can stop and potentially reverse cardiac remodeling and dysfunction linked with HF development. HDACs remove acetyl groups from nucleosomal histones, altering DNA-histone protein electrostatic interactions in the regulation of gene expression. However, HDACs also remove acetyl groups from non-histone proteins in various tissues. Changes in histone and non-histone protein acetylation plays a key role in protein structure and function that can alter other post translational modifications (PTMs), including protein phosphorylation. Protein phosphorylation is a well described PTM that is important for cardiac signal transduction, protein activity and gene expression, yet the functional role for acetylation-phosphorylation cross-talk in the myocardium remains less clear. This review will focus on the regulation and function for acetylation-phosphorylation cross-talk in the heart, with a focus on the role for HDACs and HDAC inhibitors as regulators of acetyl-phosphorylation cross-talk in the control of cardiac function.

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Section: Hdac Inhibition Protein Phosphorylation and Heart Failurementioning

confidence: 99%

The Crosstalk between Acetylation and Phosphorylation: Emerging New Roles for HDAC Inhibitors in the Heart

Habibian

Ferguson

2018

IJMS

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“…Whereas, inhibition of JNK and ERK was sufficient to attenuate gene expression of selected genes; our data do not infer that anti-inflammatory actions were solely the result of ERK and JNK signaling. With respect to the literature, in which HDACs have been shown to regulate NF-κB (S. Chen et al, 2018), JAK/STAT (S. Chen et al, 2018;Yang & Seto, 2008), MAPKs (Blakeslee et al, 2017;Ferguson et al, 2013), and PI3K/AKT (Yang & Seto, 2008) among others; we would postulate that anti-inflammatory actions mediated by HDAC inhibitors are a result of MAPK inhibition in combination with changes in other signaling cascades. Assessment of these intracellular pathways in bovine MAC-Ts would be interesting to explore.…”

Section: Discussionmentioning

confidence: 99%

HDAC1/2‐mediated regulation of JNK and ERK phosphorylation in bovine mammary epithelial cells in response to TNF‐α

Romanick

Morrill

Hostler

et al. 2018

Journal Cellular Physiology

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Bovine mammary epithelial cells (MAC-Ts) are a common cell line for the study of mammary epithelial inflammation; these cells are used to mechanistically elucidate molecular underpinnings that contribute to bovine mastitis. Bovine mastitis is the most prevalent form of disease in dairy cattle that culminates in annual losses of two billion dollars for the US dairy industry. Thus, there is an urgent need for improved therapeutic strategies. Histone deacetylase (HDAC) inhibitors are efficacious in rodent models of inflammation, yet their role in bovine mammary cells remain unclear. HDACs have traditionally been studied in the regulation of nucleosomal DNA, in which deacetylation of histones impact chromatin accessibility and gene expression. Using MAC-T cells stimulated with tumor necrosis factor α (TNF-α) as a model for mammary cell inflammation, we report that inhibition of HDACs1 and 2 (HDAC1/2) attenuated TNF-α-mediated inflammatory gene expression. Of note, we report that HDAC1/2-mediated inflammatory gene expression was partly regulated by c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation. Here, we report that HDAC1/2 inhibition attenuated JNK and ERK activation and thus inflammatory gene expression. These data suggest that HDACs1 and 2 regulate inflammatory gene expression via canonical (i.e., gene expression) and noncanonical (e.g., signaling dependent) mechanisms. Whereas, further studies using primary cell lines and animal models are needed. Our combined data suggest that HDAC1/2-specific inhibitors may prove efficacious for the treatment of bovine mastitis.

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“…KIF5A was reported to be involved in the transport of lysosomes, synaptic vesicle precursors, other diverse vesicles, and mitochondria (Morfini et al 2016). This kinesin also regulates the intracellular transport of cargo, such as autophagosomes, in cardiomyocytes (Blakeslee et al 2017). To note, the deficiency in KIF5A induces epilepsy in both humans (Dixit et al 2016) and mice (Nakajima et al 2012) and is also associated with myoclonic seizures in humans (Rydzanicz et al 2017).…”

Section: Autophagy In Tmt-induced Neurotoxicitymentioning

confidence: 99%

Autophagy in trimethyltin-induced neurodegeneration

et al. 2020

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Autophagy is a degradative process playing an important role in removing misfolded or aggregated proteins, clearing damaged organelles, such as mitochondria and endoplasmic reticulum, as well as eliminating intracellular pathogens. The autophagic process is important for balancing sources of energy at critical developmental stages and in response to nutrient stress. Recently, autophagy has been involved in the pathophysiology of neurodegenerative diseases although its beneficial (pro-survival) or detrimental (pro-death) role remains controversial. In the present review, we discuss the role of autophagy following intoxication with trimethyltin (TMT), an organotin compound that induces severe hippocampal neurodegeneration associated with astrocyte and microglia activation. TMT is considered a useful tool to study the molecular mechanisms occurring in human neurodegenerative diseases such as Alzheimer's disease and temporal lobe epilepsy. This is also relevant in the field of environmental safety, since organotin compounds are used as heat stabilizers in polyvinyl chloride polymers, industrial and agricultural biocides, and as industrial chemical catalysts.

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Class I HDACs control a JIP1-dependent pathway for kinesin-microtubule binding in cardiomyocytes

Cited by 12 publications

References 43 publications

The Crosstalk between Acetylation and Phosphorylation: Emerging New Roles for HDAC Inhibitors in the Heart

The Crosstalk between Acetylation and Phosphorylation: Emerging New Roles for HDAC Inhibitors in the Heart

HDAC1/2‐mediated regulation of JNK and ERK phosphorylation in bovine mammary epithelial cells in response to TNF‐α

Autophagy in trimethyltin-induced neurodegeneration

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