Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation - PubMed (original) (raw)

TSA and SAHA acetylate MTs and stimulate vesicular transport of BDNF through an HDAC6-dependent mechanism. A, B, WT (+/+) cells were treated for 4 h with DMSO (0.1%, control, CT), TSA (1 μ

m

), SAHA (2 μ

m

), and NaPB [10 m

m

(A, B, left) or for 16 h (B, right)] and analyzed by immunofluorescence (A) or Western blot (B) for the presence of acetylated tubulin, α-tubulin, acetylated histone H3, and histone H3. C, WT (+/+) cells were treated for 4 h with DMSO (0.1%, CT), tubacin (6 μ

m

), and MS-275 (3 μ

m

) and stained for α-tubulin, acetylated histone H3, and acetylated tubulin. D, Extracts from WT cells treated for 4 h with DMSO (0.1%, CT), MS-275 (3 μ

m

), or tubacin (6 μ

m

) were processed by Western blot and analyzed for acetylated tubulin, α-tubulin, acetylated histone H3, and histone H3. E, F, WT (+/+) cells transfected with BDNF-eGFP were treated as in D and analyzed by videomicroscopy. G, Untransfected cells and cells transfected with HDAC6WT or HDAC6m1m2 were treated with DMSO (0.1%, CT) and TSA (100 n

m

) for 4 h and immunostained with anti-HDAC6 and anti-acetylated tubulin antibodies. HDAC6WT or HDAC6m1m2 transfected cells are labeled with an asterisk. H, I, Striatal cells were cotransfected with BDNF-eGFP and with HDAC6WT, HDAC6m1m2, or the corresponding empty vector (pcDNA3), treated with DMSO (0.1%, CT) and TSA (100 n

m

) for 4 h, and analyzed by videomicroscopy. Dashed lines correspond to the control values. N.S., Not significant. *p < 0.05; **p < 0.01; ***p < 0.001.