Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is well established that prolactin (PRL) sustains, while prostaglandin F(2 alpha) (PGF(2 alpha)) curtails, progesterone production by the rat corpus luteum (CL). We have previously shown that the actions of both molecules converge on the 20 alpha-HSD gene and control its expression in a dramatically opposed manner. In this investigation, we have found twelve more genes that are inversely regulated by PRL and PGF(2 alpha). In addition to 20 alpha-HSD, PGF(2 alpha) stimulated and PRL inhibited PGF(2 alpha)-receptor, phospholipase C delta(1) and TGF beta(1) expression. In contrast PRL stimulated and PGF(2 alpha) inhibited the LH receptor, 11 beta-HSD2, sterol carrier protein 2, mitochondrial glutathione S-transferase (GST), GST mu(2), inhibitory DNA-binding proteins 1, 2, and 3, and calcium binding protein 2. We have also identified new target genes for PRL and PGF(2 alpha). PGF(2 alpha) stimulated the expression of genes involved in cell signaling such as cell adhesion kinase-beta, ERK3, FRA2, IL-2 receptor, and 14-3-3 proteins. PGF(2 alpha) also up-regulated the expression of the sodium channel beta(1), Na/K ATPase, annexin IV, GST7pi, and P450 reductase. In contrast PGF(2 alpha) inhibited the expression of two genes involved in cell cycle: cyclin D2 and retinoblastoma related protein (Rb2/p130). It also inhibited genes involved in estradiol (P-450(AROM)) and cholesterol biosynthesis (HMG-CoA synthase), as well as genes involved in tissue remodeling: VEGF and TIMP3. PRL had a profound inhibitory effect on the expression of genes encoding the ADP-ribosylation factor 3, annexin V and c-jun, yet increased the expression of P450scc, 3beta-HSD, and SR-B1 (HDL-receptor), all genes involved in steroidogenesis. PRL also stimulated the expression of beta(2)-microglobulin, TIMP2, cytochrome c oxidase IV, cathepsin H and L, and copper-zinc superoxide dismutase as well as elongation factor SIII, heat shock protein-60 and mitochondrial ATP synthase-D. In conclusion, this investigation has revealed a "yin-yang" relationship between PRL and PGF(2 alpha) in regulating certain critical genes in the rodent CL, and has demonstrated novel regulation by these factors of other important genes involved in luteal function.
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PMID:Opposite effect of prolactin and prostaglandin F(2 alpha) on the expression of luteal genes as revealed by rat cDNA expression array. 1151 96

Simvastatin has been shown to stimulate osteogenic cell differentiation. Our previous study showed osteoblasts on trabecular surface are increased by simvastatin treatment in animal study. However, whether simvastatin stimulates osteoblast proliferation and by what molecular mechanism have not been adequately investigated. Because the mitochondrial function is crucial for cell survival and proliferation, we hypothesize that simvastatin may promote human osteoblast (hOBs) proliferation and it may be related to mitochondrial function. Our results showed that simvastatin significantly enhanced proliferation and increased both mRNA and protein levels of cyclin D2, Bcl-2 and the ratio of Bcl-2 to Bax (Bcl-2/Bax). Furthermore, simvastatin increased mitochondrial activity and ATP content of hOBs. Most importantly, treatment with ATP synthase blocker, oligomycin, significantly decreased both simvastatin-stimulated ATP content and cell proliferation, and completely reversed the simvastatin-induced up-regulation of cyclin D2 and Bcl-2 expression in hOBs. On the other hand, rotenone, the complex I blocker, also partially blocked simvastatin-stimulated ATP content and cell proliferation, but the blocker did not suppress the effect of simvastatin on cyclin D2 and Bcl-2 expression. These results indicate that the up-regulation of cyclin D2 and Bcl-2/Bax by simvastatin depends on the intact function of ATP synthase in the mitochondria of hOBs. It suggests that simvastatin may promote hOB proliferation, at least partly, via up-regulating mitochondrial function and subsequently cyclin D2 and Bcl-2/Bax expression. The findings provide new information for the basic medical science in bone physiology and for new therapy strategy of simvastatin on bone formation in future.
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PMID:Simvastatin enhances human osteoblast proliferation involved in mitochondrial energy generation. 2376 41