Vascular smooth muscle cells (SMCs) generate @entity1223 (CO) via the catabolism of @entity1446 by the enzyme heme oxygenase (HO). In the present study, we found that serum stimulated a time- and concentration-dependent increase in the levels of HO-1 messenger RNA (mRNA) and protein in vascular SMCs. The induction of HO-1 expression by serum was inhibited by @entity4316 or @entity1880 . In addition, serum stimulated HO activity, as reflected by an increase in the concentration of @entity648 in the culture media. Treatment of vascular SMCs with serum stimulated DNA synthesis and this was potentiated by the HO inhibitors, @entity219 and @entity44024 as well as by the CO scavenger, hemoglobin. The @entity68 chelator @entity5532 had no effect on DNA synthesis. However, exposure of vascular SMCs to exogenous CO inhibited serum-stimulated SMC proliferation and the phosphorylation of @entity995 protein. In addition, CO arrested SMCs at the G(1)/S transition phase of the cell cycle and selectively blocked the serum-stimulated expression of @entity7596 mRNA and protein without affecting the expression of @entity4910 and E. CO also inhibited the serum-stimulated activation of @entity7596 -associated kinase activity and cyclin-dependent kinase 2 activity. These results demonstrate that serum stimulates HO-1 gene expression and CO synthesis. Furthermore, they show that CO acts in a negative feedback fashion to inhibit vascular SMC growth by regulating specific components of the cell cycle machinery. The capacity of vascular mitogens to induce CO synthesis may provide a novel mechanism by which these agents modulate cell growth.

Heme oxygenase-1-derived XXXX is an autocrine inhibitor of vascular smooth muscle cell growth.

@entity1223 :: ('MESH:D002248', 'Chemical') :: ['carbon monoxide'] @entity5532 :: ('MESH:D003676', 'Chemical') :: ['desferrioxamine'] @entity44024 :: ('MESH:C032628', 'Chemical') :: ['tin protoporphyrin-IX'] @entity1880 :: ('MESH:D003513', 'Chemical') :: ['cycloheximide'] @entity648 :: ('MESH:D001663', 'Chemical') :: ['bilirubin'] @entity219 :: ('MESH:D015032', 'Chemical') :: ['zinc'] @entity4910 :: ('595', 'Gene') :: ['cyclin D1'] @entity4316 :: ('MESH:D003609', 'Chemical') :: ['actinomycin D'] @entity995 :: ('MESH:D012175', 'Disease') :: ['retinoblastoma'] @entity7596 :: ('890', 'Gene') :: ['cyclin A'] @entity68 :: ('MESH:D007501', 'Chemical') :: ['iron'] @entity1446 :: ('MESH:D006418', 'Chemical') :: ['heme']
@entity1223 :: (MESH:D002248,Chemical) :: ['carbon monoxide']
