INT312882

Context Info Confidence 0.52 First Reported 2010 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 1 Total Number 19 Disease Relevance 1.86 Pain Relevance 0.63

cytosol (Hdac6) nucleolus (Hdac6) nucleus (Hdac6) intracellular (Hdac6) protein complex (Hdac6) cytoplasm (Hdac6)

Anatomy Link Frequency neurons 5 Brain 1 Hdac6 (Rattus norvegicus)

Pain Link Frequency Relevance Heat imagery 95 95.32 sSRI 38 90.92 Serotonin 38 90.36 fluoxetine 57 89.24 depression 19 70.48 agonist 38 66.24 cerebral cortex 19 14.48 Hippocampus 19 12.88

Disease Link Frequency Relevance Heat Disease 266 98.00 Targeted Disruption 19 89.84 Neurodegenerative Disease 38 86.60 Depression 19 70.48 Stress 19 41.36 Infection 38 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

We found that the presence of tubacin, a specific HDAC6 inhibitor, dramatically enhanced mitochondrial movement in hippocampal neurons, whereas niltubacin, an inactive tubacin analog, had no effect.

Negative_regulation (inhibitor) of HDAC6 in neurons

1) Confidence 0.52 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2877100 Disease Relevance 0 Pain Relevance 0.05

inhibitors resulted in a slight decrease of HDAC6 protein level (Fig. 4A, B).

Negative_regulation (decrease) of HDAC6

2) Confidence 0.52 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0 Pain Relevance 0

Consistent with this idea, it was recently reported that inhibition of HDAC6 produced a higher transfection efficiency by enhancing intracellular transport of transfected plasmids [22].

Negative_regulation (inhibition) of HDAC6

3) Confidence 0.52 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0 Pain Relevance 0

Inhibition of HDAC6 increases acetylation of tubulin and association of kinesin-1 with mitochondria in hippocampal neurons

Negative_regulation (Inhibition) of HDAC6 in neurons

4) Confidence 0.52 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0 Pain Relevance 0.05

Inhibition of HDAC6 results in higher levels of acetylated tubulin and enhanced binding of the motor protein kinesin-1 to tubulin, which promotes transport of cargoes along microtubules.

Negative_regulation (Inhibition) of HDAC6

5) Confidence 0.52 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2877100 Disease Relevance 0 Pain Relevance 0.04

In the present study, we show that specific inhibition of HDAC6 greatly enhances mitochondrial trafficking in cultured hippocampal neurons.

Negative_regulation (inhibition) of HDAC6 in neurons

6) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0.60 Pain Relevance 0

Inhibition of HDAC6 by tubacin greatly increases mitochondrial movement

Negative_regulation (Inhibition) of HDAC6

7) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0.43 Pain Relevance 0

As shown by Western blot analysis, inhibition of HDAC6 by tubacin increased the amount of kinesin-1 associated with mitochondria compared to an untreated control (Fig. 2E, lanes 1 and 2).

Negative_regulation (inhibition) of HDAC6

8) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0 Pain Relevance 0.03

Here, we demonstrate that inhibition of HDAC6 affects mitochondrial trafficking in a manner similar to that of GSK3?

Negative_regulation (inhibition) of HDAC6

9) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0.47 Pain Relevance 0

We suggest that 5-HT promotes axonal transport of mitochondria in a manner similar to that of HDAC6 inhibition.

Negative_regulation (inhibition) of HDAC6

10) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0 Pain Relevance 0.17

These results closely resemble the effects of inhibiting HDAC6 using tubacin or TSA (Fig. 2A, lanes 2 and 3; Fig. 2E, lanes 2 and 3).

Negative_regulation (inhibiting) of HDAC6

11) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0 Pain Relevance 0

Moreover, Dompierre et al. [5] found that inhibiting HDAC6 reversed the transport deficit in a Huntington's disease model by increasing the vesicular transport of Brain-Derived Neurotrophic Factor (BDNF), another kinesin-1 cargo protein.

Negative_regulation (inhibiting) of HDAC6 in Brain associated with disease

12) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0.10 Pain Relevance 0

inhibition and HDAC6 activity are closely linked.

Negative_regulation (inhibition) of HDAC6

13) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0.26 Pain Relevance 0.16

Specific inhibition of HDAC6 leads to increased mitochondrial motility

Negative_regulation (inhibition) of HDAC6

14) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0 Pain Relevance 0.10

Since kinesin-1 is not an exclusively mitochondrial motor protein, it is likely that the observed effect of increased acetylation of microtubules on mitochondrial movement produced by inhibiting HDAC6 is a reflection of a more general promotion of intracellular cytoplasmic trafficking within neurons.

Negative_regulation (inhibiting) of HDAC6 in neurons

15) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0 Pain Relevance 0

decreases the activity and protein levels of HDAC6 in hippocampal neurons

Negative_regulation (decreases) of HDAC6 in neurons

16) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0 Pain Relevance 0

In contrast, niltubacin (20 µM), a tubacin analog that neither inhibits HDAC6 nor enhances acetylation of microtubules [14], did not alter mitochondrial movement (Fig. 1C, F, I and Movies S7, S8, S9).

Negative_regulation (inhibits) of HDAC6

17) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0 Pain Relevance 0.04

This was demonstrated by preventing tubulin deacetylation with tubacin, a specific HDAC6 inhibitor.

Negative_regulation (inhibitor) of HDAC6

18) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0 Pain Relevance 0

Under pathological circumstances, the effect of HDAC6 on the degradation of misfolded-protein may also be involved in mitochondrial trafficking.

Negative_regulation (effect) of HDAC6

19) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2877100 Disease Relevance 0 Pain Relevance 0

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