Expression of trypsin-like proteases and protease nexin-1 in mdx mouse muscles.
In order to examine the possible participation of trypsin-like proteases in the onset and progress of muscular dystrophy, we investigated the expression of the trypsin-like protease in muscular tissues in mdx mice. We found that the mRNAs of several trypsin-like proteases, including hepsin and t-PA, were expressed in the muscular tissues of mdx mice, but at levels not significantly different from normal mice. Since the enzymatic properties of dystrypsin, a muscle trypsin-like protease activated before onset of the disease, are similar to those of thrombin, we investigated the expression pattern of thrombin in mdx mouse muscles. The results showed that prothrombin mRNA is up-regulated in mdx mice at 20-30 days of age but not before the age of 15 days (preclinical). Since protease nexin-1 (PN-1) is known to be a physiological inhibitor of thrombin, we also examined the expression pattern of PN-1. We found that PN-1 transcription and translation is down-regulated in the muscular tissues of mdx mice, before the onset of clinical symptoms. These results suggest that thrombin may be involved in the progression of muscular dystrophy or the regeneration of muscle fibers after the onset of the disease and that the reduced level of PN-1 may enhance the activities stimulate the activities of muscle proteases, including dystrypsin, at a preclinical stage in mdx mice.
Sawada
Hitoshi
H
Sugashima Marine Biological Laboratory, Graduate School of Science, Nagoya University, 517-0004 Toba, Japan. hsawada@bio.nagoya-u.ac.jp
Kikukawa
Yuhsuke
Y
Ban
Susumu
S
Kakudo
Tomoyuki
T
Yokosawa
Hideyoshi
H
D000375:Aging; D016564:Amyloid beta-Protein Precursor; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis*; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D015536:Down-Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009121:Muscle Denervation; D024510:Muscle Development; D009132:Muscles / Q000201:enzymology*; D009137:Muscular Dystrophy, Animal / Q000378:metabolism; D058255:Protease Nexins; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D012697:Serine Endopeptidases / Q000096:biosynthesis; D013917:Thrombin / Q000037:antagonists & inhibitors; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014357:Trypsin / Q000096:biosynthesis* / Q000737:chemistry; D015854:Up-Regulation
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D058255:Protease Nexins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D012697:Serine Endopeptidases; C055645:hepsin; D014357:Trypsin; D013917:Thrombin; C083866:T103N, KHRR 296-299 AAAA; D010959:Tissue Plasminogen Activator