Leupeptin-sensitive proteases involved in cell survival after X-ray irradiation in human RSa cells.
Proteases have received attention as important cellular components responsible for stress response in human cells. However, little is known about the role of proteases in the early steps of cell response after X-ray irradiation. In the present study, we first searched for proteases whose activity levels are changed soon after X-ray irradiation in human RSa cells with a high sensitivity to X-ray cell-killing. RSa cells showed an increased level of fibrinolytic protease activity within 10 min after irradiation with X-ray (up to 3 Gy). The induced protease activity was proved to be inhibited by leupeptin. We next examined whether this protease inducibility is related to the X-ray susceptibility of cells. Treatment of RSa cells with leupeptin prior to X-ray irradiation resulted in lowered colony survival and an increased ratio of G(2)/M-arrested cells and apoptotic cells. These results suggest that leupeptin-sensitive proteases are involved in the resistance of human RSa cells to X-ray cell-killing.
Zhang
Hong-Chang
HC
Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, Chuoku, Japan.
Karata
Kiyonobu
K
Matsushita
Kazuyuki
K
Takahashi
Shunji
S
Tong
Xiao-Bo
XB
Lu
Jun
J
Zhu
Chang-Lin
CL
Sugaya
Shigeru
S
Suzuki
Toshikazu
T
Suzuki
Nobuo
N
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D019008:Drug Resistance, Neoplasm; D005342:Fibrinolysis / Q000187:drug effects / Q000528:radiation effects; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D014965:X-Rays
D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D010447:Peptide Hydrolases; C032854:leupeptin