Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PCR and Southern blot analyses demonstrate that mRNA for heme oxygenase (HO), a well known "stress protein" in a number of tissues, is present in human retina. Western and northern blots show that the protein and mRNA are also expressed in human Y-79 retinoblastoma cells in culture and that the HO enzyme is rapidly induced by its substrate, heme. Moreover, HO is also induced by two chemicals, sodium arsenite and menadione, that act as agents of oxidative stress. HO is the regulatory enzyme in the heme degradative pathway and an increase in its activity could lead to the accumulation of bilirubin, an antioxidant, in the cell at the expense of heme, a prooxidant. The HO pathway may thus be of importance in protecting the retina against oxidative stress in vivo. Moreover, the Y-79 culture system should provide an excellent model for use in examining stress mechanisms in retinal cells at a molecular level.
 ...
PMID:Heme oxygenase: expression in human retina and modulation by stress agents in a human retinoblastoma cell model system. 157 5

Vascular smooth muscle cells (SMCs) generate carbon monoxide (CO) via the catabolism of heme 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 actinomycin D or cycloheximide. In addition, serum stimulated HO activity, as reflected by an increase in the concentration of bilirubin in the culture media. Treatment of vascular SMCs with serum stimulated DNA synthesis and this was potentiated by the HO inhibitors, zinc and tin protoporphyrin-IX as well as by the CO scavenger, hemoglobin. The iron chelator desferrioxamine had no effect on DNA synthesis. However, exposure of vascular SMCs to exogenous CO inhibited serum-stimulated SMC proliferation and the phosphorylation of retinoblastoma 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 cyclin A mRNA and protein without affecting the expression of cyclin D1 and E. CO also inhibited the serum-stimulated activation of cyclin A-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.
 ...
PMID:Heme oxygenase-1-derived carbon monoxide is an autocrine inhibitor of vascular smooth muscle cell growth. 1203 74

Multiple myeloma (MM) is a hematological malignancy that is characterized by the clonal expansion of plasma cells in the bone marrow. Histone deacetylases (HDACs) represent a new type of molecular targeted therapy for different types of cancers and promising targets for myeloma therapy. We showed that HDAC3 mRNA and protein levels of CD138 mononuclear cells from MM patients were higher than those in healthy donors. Therefore, we investigated the effects of a novel class I HDAC inhibitor BG45 on MM cells in vitro. BG45 downmodulated heme oxygenase 1 (HO-1) when class I HDACs decreased in MM cells. HO-1 is a target for the treatment of MM. Moreover, BG45 induced hyperacetylation of histone H3 and inhibited the growth, especially the apoptosis of MM cell lines. Treatment with BG45 induced apoptosis by downregulating bcl-2 and Bcl-xl, upregulating Bax and other antiapoptotic proteins and activating poly(ADP-ribose)polymerase, and decreasing protein levels of p-JAK2 and p-STAT3. These effects were partly blocked by HO-1. Correspondingly, BG45 led to an accumulation in the G0/G1 phase, accompanied by decreased levels of CDK4 and phospho-retinoblastoma protein, an increased level of p21, and a moderately reduced level of CDK2. Clinical use of single agents was limited because of toxic side effects and drug resistance. However, combining BG45 with lenalidomide exerted synergistic effects. In conclusion, we verified the potent antimyeloma activity of this novel HDAC inhibitor and that the combination of BG45 and lenalidomide is a new method for MM treatment. Thus, BG45 may be applicable to the treatment of MM and other hematological malignancies.
 ...
PMID:Histone deacetylase inhibitor BG45-mediated HO-1 expression induces apoptosis of multiple myeloma cells by the JAK2/STAT3 pathway. 2904 36