Low and high molecular weight poly(l‐lysine)s/poly(l‐lysine)–DNA complexes initiate mitochondrial‐mediated apoptosis differently

摘要: Poly(L-lysine)s, PLLs, are commonly used for DNA compaction and cell transfection. We report that, although PLLs of low (2.9 kDa), L-PLL, high (27.4 H-PLL, Mw in free form DNA-complexed cannot only cause rapid plasma membrane damage human lines, phosphatidylserine "scrambling" loss integrity, but later (24 h) initiate stress-induced death via mitochondrial permeabilization without the involvement processed caspase-2. Mitochondrially mediated apoptosis was confirmed by detection cytochrome c (Cyt c) release, activation caspases-9 -3, subsequent changes potential. Plasma were most prominent with H-PLL. Cytoplasmic level Cyt more elevated following H-PLL treatment, unlike L-PLL case, inhibition Bax channel-forming activity reduced extent release from mitochondria half. Inhibition had no modulatory effect on L-PLL-mediated release. Further, functional studies isolated indicate that not can directly induce depolarization, a progressive decline rate uncoupled respiration. Combined, our data suggest capable initiating mitochondrially differently. The observed PLL-mediated late-phase may provide an explanation previously reported transient gene expression associated PLL-based transfection vectors. importance relation to design novel safer cationic non-viral vectors therapy is discussed.