Abstract
The role of newly synthesized proteins in the activation of the NO pathway was investigated by evaluating the effects of the protein synthesis inhibitor cycloheximide (CHX) on basal and lipopolysaccharide (LPS-) induced cGMP accumulation in rat aortic smooth muscle cells (RASM). Pretreatment of RASM with 10 µM CHX for 24 h resulted in a 10-fold increase in cGMP. Inclusion of an inhibitor of NO synthase NG-monomethyl-L-arginine (LNMMA, 1 mM), inhibited CHX-induced cGMPG formation (85±8 vs 266±55) pmol/mg protein). L-arginine (10 mM), the substrate of NO synthase, potentiated cGMP accumulation and reversed the inhibitory effect of LNMMA (981±87 and 79±49 pmol/mg protein, respectively), but had no effect on baseline cGMP. LPS produced a time-dependent increase in cGMP levels with maximal stimulation at 6 h and a decline to baseline at 24 h. CHX attenuated the LPS-induced cGMP accumulation at 3 and 6 hours, however, cGMP levels were superinduced by 10-fold at later time points. CHX also shifted the LPS concentration curve 20 times to the left. The concentration-dependence of cGMP stimulation by CHX was biphasic both in the absence and presence of LPS, with maximal stimulation at 10 µM and inhibition at higher concentrations. These results show the dual role of protein synthesis in NO synthase activation and suggest the involvement of labile repressors in the regulation of NO pathway in aortic smooth muscle cells. (Supported by HL 31422).
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© 1996 Plenum Press, New York
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Go, C., Marczin, N., Dienes-Kadi, I., Snead, C., Catravas, J.D. (1996). Protein Synthesis Inhibition Induces No Synthase Activity in Vascular Smooth Muscle Cells. In: Catravas, J.D., Callow, A.D., Ryan, U.S. (eds) Vascular Endothelium. NATO ASI Series, vol 281. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0355-8_40
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DOI: https://doi.org/10.1007/978-1-4613-0355-8_40
Publisher Name: Springer, Boston, MA
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