Figure 1

HDAC inhibition drives peroxisome biogenesis in lymphoma model systems. (a) PEX3,PEX11B, and PMP70 mRNA expression profiles relative to vehicle (DMSO) in Vor-treated U937 (2 μM, 12 h), OCI-LY8 (4 μM, 12 h), and SU-DHL4 (1 μM, 12 h) cells, versus 36B4 (housekeeping control). Graphs represent means±S.E.M. (unpaired t-test) of N=4 replicates (technical triplicate). (b) Immunoblots of PEX3, PEX11B, PMP70, and β-actin (loading control) for vehicle, and 6 and 12 h Vor-treated cells. (c) PMP70 immunofluorescence (TO-PRO-3 nuclear stain) in vehicle and Vor-treated (2 μM, 12 h) cells, puncta quantitation on right. Scale bar represents 10 μm. Graph represents means±S.E.M. (unpaired t-test) of N=2 with 5 images per condition and ~5 cells per image. (d) Left: schematic of plasmalogen biosynthesis. 1-O-alkyl Dihydroxyacetone phosphate (DHAP) is exported to the ER whereby additional enzymatic reactions occur. sn-1 and sn-2 denote carbon groups, whereas the head group is shown on bottom. Note: sn-1 position is larger/bold and colored blue to indicate the plasmalogen species being examined. Right: total PlsEtn levels (pmol) in vehicle and Vor-treated (2 μM, 12 h) U937 cells. Graph represents means±S.E.M. (one-way analysis of variance, Tukey) of N=2 in technical triplicate. *P⩽0.05, **P⩽0.01, and ***P⩽0.001