Histone deacetylase 4 and 5 translocation elicited by microsecond pulsed electric field exposure is mediated by kinase activity

Electroporation-based technologies using microsecond pulsed electric field (mu sPEF) exposures are established as laboratory and clinical tools that permeabilize cell membranes. We demonstrate a mu sPEF bioeffect on nucleocytoplasmic import and export of enzymes that regulate genetic expression, histone deacetylases (HDAC) -4 and -5. Their mu sPEF-induced nucleocytoplasmic transport depends on presence and absence of extracellular calcium ions (Ca2+) for both MCF7 and CHO-K1 cells. Exposure to 1, 10, 30 and 50 consecutive square wave pulses at 1 Hz and of 100 mu s duration with 1.45 kV/cm magnitude leads to translocation of endogenous HDAC4 and HDAC5. We posit that by eliciting a rise in intracellular Ca2+ concentration, a signaling pathway involving kinases, such as Ca2+/CaM-dependent protein kinase II (CaMKII), is activated. This cascade causes nuclear export and import of HDAC4 and HDAC5. The potential of mu sPEF exposures to control nucleocytoplasmic transport unlocks future opportunities in epigenetic modification.

Automated summary

This study demonstrates the impact of microsecond pulsed electric fields on nucleocytoplasmic transport of HDAC4 and HDAC5, which is dependent on the presence of extracellular calcium ions. By inducing an increase in intracellular Ca2+ concentration, a signaling pathway is activated, leading to the nuclear export and import of HDAC4 and HDAC5. This research opens up new opportunities in the field of epigenetic modification.