Histone H1.2 is translocated to mitochondria and associates with Bak in bleomycin-induced apoptotic cells.
Bleomycin induces single- and double-stranded breaks in DNA, with consequent mitochondrial membrane aberrations that lead to the apoptotic cell death. It is poorly understood how DNA damage-inducing apoptotic signals are transmitted to mitochondria, from which apoptotic factors are released into the cytoplasm. Here, we investigated the localization of histone H1.2 in the bleomycin-treated human squamous carcinoma SCCTF cells. The presence of DNA double-strand breaks in the bleomycin-treated cells was examined by Western analysis using antibody against phosphorylated histone H2AX (gamma-H2AX). Incubation of SCCTF cells for 48 h with 10 microM bleomycin induced apoptosis, as determined by cleavage of lamin B1 to 28 kDa fragment and DNA ladder formation. The mitochondrial permeabilization causing apoptotic feature was also detected with MitoCapture in the bleomycin-treated cells. Histone H1.2 was translocated from the nucleus to the mitochondria after treatment with bleomycin and co-localized with Bak in mitochondria. Our present results suggest that histone H1.2 plays an important role in transmitting apoptotic signals from the nucleus to the mitochondria following double-stranded breaks of DNA by bleomycin.
Okamura
Hirohiko
H
Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima 770-8504, Japan. okamura@dent.tokushima-u.ac.jp
Yoshida
Kaya
K
Amorim
Bruna Rabelo
BR
Haneji
Tatsuji
T
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001761:Bleomycin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D053904:DNA Breaks, Single-Stranded / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; C494772:BAK1 protein, human; D006657:Histones; C478221:LAMB1 protein, human; D007797:Laminin; D050998:bcl-2 Homologous Antagonist-Killer Protein; D001761:Bleomycin