REGIOSELECTIVITY ENHANCEMENT BY PARTIAL-PURIFICATION OF LIPASE FROM ASPERGILLUS-NIGER

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Title:	REGIOSELECTIVITY ENHANCEMENT BY PARTIAL-PURIFICATION OF LIPASE FROM ASPERGILLUS-NIGER
Authors:	CHEN, HP;HSIAO, KF;WU, SH;WANG, KT
Contributors:	醫學院醫學系生化學科;ACAD SINICA,INST BIOL CHEM,TAIPEI,TAIWAN;CHINA MED COLL,DEPT BIOCHEM,TAICHUNG,TAIWAN;NATL TAIWAN UNIV,DEPT CHEM,TAIPEI 10764,TAIWAN
Date:	1995
Issue Date:	2010-09-24 14:52:49 (UTC+8)
Publisher:	CHAPMAN HALL LTD
Abstract:	An indazole derivative, YC-1, was identified in this study to be capable of reversibly and effectively inhibiting proliferation of rat A10 vascular smooth-muscle cells (VSMCs) in vitro. YC-1 (1-100 mu M) dose-dependently inhibited [H-3]thymidine incorporation into DNA in rat A10 VSMCs that were synchronized by serum depletion and then restimulated by addition of 10% foetal calf serum (FCS), whereas FCS-induced [H-3]thymidine incorporation into rat synchronized endothelial cells was unaffected by this agent. The dose of YC-1 required to cause inhibition of FCS-induced proliferation was similar to that necessary for the formation of cellular cyclic GMP (cGMP). Guanylate cyclase activity in soluble fractions of VSMCs was activated by YC-1 (1-100 mu M), whereas cGMP-specific phosphodiesterase activity was unaffected by this compound. The anti-proliferative effect of YC-1 was mimicked by 8-bromo-cGMP, a membrane-permeable cGMP analogue, and was antagonized by KT 5823 (0.2 mu M), a selective inhibitor of protein kinase G. The anti-proliferative effect of YC-1 was also antagonized by Methylene Blue (50 mu M), a guanylate cyclase inhibitor, and was potentiated by 3-isobutyl-1-methylxanthine (500 mu M), a phosphodiesterase inhibitor. These results verified that YC-1 is a direct soluble guanylate cyclase activator in A10 VSMCs, and the anti-proliferative effect of YC-1 is mediated by cGMP. YC-1 still inhibited FCS-induced DNA synthesis even when added 10-18 h after restimulation of the serum-deprived A10 VSMCs with 10% FCS. Flow cytometry in synchronized populations revealed an acute blockage of FCS-inducible cell-cycle progression at a point in the G(1)/S-phase in YC-1 (100 mu M)-treated cells. The inhibition of proliferation by YC-1 was demonstrated to be independent of cell damage, as documented by several criteria of cell viability. In conclusion, YC-1 reversibly and effectively inhibited the proliferation of VSMCs,suggesting that it has potential as a therapeutic agent in the prevention of vascular diseases.
Relation:	BIOTECHNOLOGY LETTERS 17(3):305-308
Appears in Collections:	[School of Medicine] Journal articles

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