Caspase-resistant vimentin suppresses apoptosis after photodynamic treatment with a silicon phthalocyanine in Jurkat cells.
Oxidative stress, such as photodynamic therapy, is an apoptosis inducer. Apoptosis, as well as photosensitization, have been associated with disruption of the cytoskeletal network. The purpose of the present study was to assess the role of vimentin, a major cytoskeletal protein, in apoptosis after photodynamic treatment (PDT) with the silicon phthalocyanine Pc 4 in human Jurkat T cells. Here we show for the first time that photosensitization with Pc 4 initiates vimentin cleavage and that this event precedes poly(ADP-ribose) polymerase (PARP) degradation. Similar findings were obtained in the presence of C2-ceramide, an inducer of oxidative stress and apoptosis. In the presence of benzyloxycarbonyl-Val-Ala-Asp(O-methyl)-fluoromethylketone, a pan-caspase inhibitor, Pc 4-PDT-induced vimentin and PARP cleavage were abolished. In Jurkat cells transfected with a caspase-resistant vimentin apoptosis was partly suppressed and delayed post-Pc 4-PDT. We suggest that the full-length vimentin confers resistance to nuclear apoptosis after PDT with Pc 4.
Belichenko
I
I
Department of Radiation Oncology, Case Western Reserve University School of Medicine, Cleveland, Ohio, 44106-4942, USA.
Morishima
N
N
Separovic
D
D
D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D019169:Jurkat Cells; D017646:Organosilicon Compounds / Q000494:pharmacology*; D018384:Oxidative Stress; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012821:Silanes; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014162:Transfection; D014746:Vimentin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D007211:Indoles; C064769:N-acetylsphingosine; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents; D012821:Silanes; D014746:Vimentin; C082854:silicon phthalocyanine; C052464:bis(tri-n-hexylsiloxy)(2,3-naphthalocyaninato)silicon; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D013110:Sphingosine