Dimethylarsinic acid exposure causes accumulation of Hsp72 in cell nuclei and suppresses apoptosis in human alveolar cultured (L-132) cells.
We previously found that 72-kDa heat shock protein (Hsp72) was induced and accumulated in the nuclei, together with DNA damage, in human alveolar epithelial (L-132) cells by exposure to dimethylarsinic acid (DMAA), which is a main metabolite of inorganic arsenics in mammals. In the present study, the intracellular behavior of Hsp72 was investigated during the recovery from the DNA damage induced by exposure to DMAA. L-132 cells were exposed to 10 mM DMAA for 3 h, and then incubated in DMAA-free medium. The induction of Hsp72 by exposure to DMAA reached a peak at 6-9 h after removal of DMAA. However, the cell-nuclear distribution of Hsp72 was observed until 3 h after the start of DMAA-free incubation. We further investigated the appearance of apoptosis of L-132 cells after exposure to 10 mM DMAA for 3 h. Internucleosomal DNA fragmentation and morphological changes, as criteria for the evidence of apoptosis, were observed 6-22 h after the start of DMAA-free incubation. The appearance of apoptosis was followed by the release of Hsp72 from the cell nuclei. These results suggest a possibility that the cell-nuclear Hsp72 may suppress the appearance of apoptosis in DNA-damaged cells.
Kato
K
K
Nihon University College of Pharmacy,Funabashi, Chiba, Japan.
Yamanaka
K
K
Hasegawa
A
A
Okada
S
S
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002101:Cacodylic Acid / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D004591:Electrophoresis, Polyacrylamide Gel; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D006801:Humans; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D002101:Cacodylic Acid