Induction of tissue-type plasminogen activator and 72-kDa type-IV collagenase by ionizing radiation in rat astrocytes.
Radiation-induced damage in the central nervous system (CNS) is believed to be targeted to glial or endothelial cells or both, although the pathophysiology of the process is still poorly understood. In this study, we irradiated rat astrocytes with single doses of X-rays and then estimated the levels of tissue plasminogen activator (tPA) and collagenase in serum-free medium and cell extracts at different times. Fibrin zymography revealed increased levels of intracellular tPA activity at 12 hr after irradiation. Gelatin zymography showed continuously increasing levels of extracellular 72-kDa type-IV collagenase after irradiation. Quantitative enzymatic activities by densitometry showed a 3- to 4-fold elevation in the level of the intracellular tPA activity at 12 hr and a 5- to 6-fold increase in the level of the extracellular 72-kDa type-IV collagenase activity at 48 hr. An ELISA with specific antibodies for tPA and 72-kDa type-IV collagenase indicated a 5-fold increase in the level of tPA at 12 hr and a more-than-7-fold increase in the level of 72-kDa type-IV collagenase at 48 hr. This study adds considerable credibility to the proposed role of plasminogen activators and type-IV collagenase in the development of CNS damage after radiotherapy for brain tumors.
Sawaya
R
R
Department of Neurosurgery, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Tofilon
P J
PJ
Mohanam
S
S
Ali-Osman
F
F
Liotta
L A
LA
Stetler-Stevenson
W G
WG
Rao
J S
JS
D000818:Animals; D001253:Astrocytes / Q000201:enzymology* / Q000528:radiation effects*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D017364:Collagenases / Q000096:biosynthesis* / Q000528:radiation effects; D005110:Extracellular Space / Q000201:enzymology; D005342:Fibrinolysis / Q000502:physiology; D007424:Intracellular Fluid / Q000201:enzymology; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism / Q000528:radiation effects; D011839:Radiation, Ionizing; D051381:Rats; D017207:Rats, Sprague-Dawley; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis* / Q000528:radiation effects
D010959:Tissue Plasminogen Activator; D017364:Collagenases; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9