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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tamoxifen (TX), an oestrogen antagonist, was used to characterize the protective effect of oestradiol (E2) on exercise-related creatine kinase (CK) release from skeletal muscle of the rat. Subcutaneous administration of TX for 3 weeks in female rats had a profound antioestrogen effect as evidenced by a reduced weight of the uterus. The CK release after electrical stimulation of the isolated soleus muscle, previously shown to be E2-dependent, was markedly reduced (30-50%) after treatment with TX; this observation points to an E2-like protective action of TX instead of E2-antagonism. This effect was dose-dependent (0.25-1.00 mg/kg) and was not seen when TX was given shortly (24 h) before the experiments. In ovariectomized females, that show more CK leakage due to the lack of circulating E2, both E2- and TX-treatment resulted in a 60% reduction of the CK leakage. Muscles from male rats, treated with TX, showed a similar response: after contractions the CK release was significantly lower. We conclude that TX, like E2, reduces contraction-induced muscle damage in the rat and, thus, has E2-agonistic properties on skeletal rat muscle.
J Steroid Biochem Mol Biol 1991
PMID:Tamoxifen and oestrogen both protect the rat muscle against physiological damage. 195 66

We have demonstrated previously that 17 beta-estradiol (E2) stimulates proliferation of skeletal tissues, both in vivo and in vitro, as measured by increased DNA synthesis and creatine kinase (CK) specific activity. The effect of E2 on bone is sex specific. E2 is active only in females and androgens only in males. By contrast, in cartilage of both sexes, dihydrotestosterone (DHT) as well as E2 stimulates CK specific activity and DNA synthesis. In bone, we find that sex steroids stimulate skeletal cell proliferation in gonadectomized as well as in immature rats. Ovariectomized (OVX) rats, between 1 and 4 weeks after surgery, show stimulation of CK by E2. The basal activity and response of CK changes with the varying endogenous levels of E2 in cycling rats, in which the highest basal activity is at proestrus and estrus and the highest response is in diestrus. In rats of all ages tested, both the basal and stimulated specific activity of CK is higher in diaphysis and epiphysis than in the uterus, or in the adipose tissue adjacent to the uterus, which has a response similar to that of the uterus itself. The effect of E2 in vivo, and in chrondroblasts and osteoblasts in vitro, is inhibited by high levels of the antiestrogen tamoxifen which, by itself, in similar high concentrations, shows stimulatory effects. In addition to the sex steroids, skeletal cells are also stimulated by secosteroid and peptide calciotrophic hormones. The interactions of the sex steroids with these hormones modulate the response of cartilage and bone cells to both sex steroids and the other calciotrophic hormones. These results provide the first steps towards understanding the regulation of bone cell proliferation and growth by the concerted action of a variety of hormones and growth factors.
J Steroid Biochem Mol Biol 1991
PMID:Regulation of proliferation of rat cartilage and bone by sex steroid hormones. 195 69

The clonal rat rhabdomyosarcoma cell line BA-HAN-1C is composed of proliferating mononuclear cells, some of which spontaneously fuse to terminally differentiated myotube-like giant cells. Both the induction of differentiation by retinoic acid (RA) and by sodium butyrate (NaBut), as well as the inhibition of proliferation by fetal calf serum (FCS)-depleted medium uniformly resulted in the same effects. There was a significant (p less than 0.001) inhibition of proliferation and induction of cellular differentiation, as evidenced by a significant (p less than 0.05) increase in creatine kinase activity. Furthermore, after exposure to RA-supplemented or FCS-depleted medium, a significant (p less than 0.001) increase in the number of myotube-like giant cells was observed. These effects were preceded by a uniform enhancement of c-raf mRNA expression, which became evident 6 h after exposure to RA, NaBut and FCS-depleted media. C-raf mRNA expression persisted at an elevated level throughout the observation period of 5 days after exposure to RA or NaBut, whereas the increased expression of c-raf mRNA observed after FCS-depletion declined near to the basal level after only 24 h. Furthermore, a transient c-fos mRNA expression was observed 15 and 30 min after exposure to RA-supplemented and FCS-depleted medium but not after exposure to NaBut. The present results suggest a possible role of c-raf in the regulation of differentiation and proliferation of this cell line. Since all our experiments with RA, NaBut and FCS-depletion resulted in an early peak of c-raf mRNA expression, it is suggested that this early peak may be sufficient to trigger events crucial for differentiation and proliferation of BA-HAN-1C tumor cells.
Virchows Arch B Cell Pathol Incl Mol Pathol 1990
PMID:Uniform response of c-raf expression to differentiation induction and inhibition of proliferation in a rat rhabdomyosarcoma cell line. 198 May 57

A sequence-specific DNA-binding protein from skeletal-muscle extracts that binds to probes of three muscle gene DNA elements is identified. This protein, referred to as muscle factor 3, forms the predominant nucleoprotein complex with the MCAT gene sequence motif in an electrophoretic mobility shift assay. This protein also binds to the skeletal actin muscle regulatory element, which contains the conserved CArG motif, and to a creatine kinase enhancer probe, which contains the E-box motif, a MyoD-binding site. Muscle factor 3 has a potent sequence-specific, single-stranded-DNA-binding activity. The specificity of this interaction was demonstrated by sequence-specific competition and by mutations that diminished or eliminated detectable complex formation. MyoD, a myogenic determination factor that is distinct from muscle factor 3, also bound to single-stranded-DNA probes in a sequence-specific manner, but other transcription factors did not. Multiple copies of the MCAT motif activated the expression of a heterologous promoter, and a mutation that eliminated expression was correlated with diminished factor binding. Muscle factor 3 and MyoD may be members of a class of DNA-binding proteins that modulate gene expression by their abilities to recognize DNA with unusual secondary structure in addition to specific sequence.
Mol Cell Biol 1991 Apr
PMID:Identification of single-stranded-DNA-binding proteins that interact with muscle gene elements. 200 90

Brain creatine kinase is a major enzyme of cellular energy metabolism. It is overexpressed in a wide range of tumor cell lines and is used as a tumor marker. We reported recently that the promoter of the human gene has a strong sequence similarity to the adenovirus E2E promoter. This similarity suggested that the brain creatine kinase gene may be regulated by the viral activator E1a. Experiments reported here showed that both enzyme activity and mRNA levels were induced by the oncogenic products of the E1a region of adenovirus type 5, but unlike the viral E2E promoter, which is induced predominantly by E1a domain 3, brain creatine kinase induction required domains 1 and 2. These domains are important for transformation and for the association of E1a with the retinoblastoma gene product and other cellular proteins. The induction by an oncogene of a cellular gene for energy metabolism may be of significance for the metabolic events that take place after oncogenic activation.
Mol Cell Biol 1990 Apr
PMID:Induction of a cellular enzyme for energy metabolism by transforming domains of adenovirus E1a. 213 6

The urinary bladder depends on intracellular ATP for the support of a number of essential intracellular processes including contraction. The concentration of ATP is maintained constant primarily via the rapid transfer of a phosphate from creatine phosphate (CP) to ADP catalyzed by the enzyme creatine kinase (CK). Since muscular pathologies associated with diabetes are in part related to intracellular alterations in metabolism, we have characterized the CK activity in both skeletal muscle and urinary bladder from control and streptozotocin-diabetic rats. The following is a summary of the results: 1) Bladder tissue from control rats showed linear kinetics with a Vmax = 390 nmoles/mg protein/min, and a Km = 275 microM. 2) Urinary bladder tissue isolated from diabetic rats displayed biphasic kinetics with Vmax = 65 and 324 nmoles/mg protein/min, and Km's = 10 microM and 190 microM respectively. 3) Skeletal muscle isolated from control rats showed linear kinetics with an approximate Vmax of 800 nmoles/mg protein/min and a Km of 280 microM CP. 4) Homogenates of skeletal muscle from diabetic rats showed complex kinetics not separable into distinct component forms. 5) The Km for ADP for both skeletal muscle and bladder was approximately 10 microM. These studies demonstrate that whereas bladders isolated from both control and diabetic rats possess a low-affinity isomer(s) of CK with similar maximum enzymatic activity, there is a high affinity isomer present within the urinary bladder muscle of diabetic rats that is not present in bladder tissue isolated from control rats. Skeletal muscle isolated from both diabetic and control rats exhibited a maximal activity 2 to 3 times higher than that of the bladder.
Mol Cell Biochem 1990 Sep 21
PMID:Creatine kinase activity of urinary bladder and skeletal muscle from control and streptozotocin-diabetic rats. 214 63

BC3H-1 mouse muscle cells in culture were employed to study the mechanisms which regulate insulin receptor gene expression during differentiation. When BC3H-1 myoblasts were plated in low serum media (1% fetal bovine serum), cell division ceased. Within 1 week cells had the morphological features of myocytes and expressed muscle specific proteins such as creatine phosphokinase and the nicotinic acetylcholine receptor. It is known that following incubation in low serum media, the steady state mRNA levels for the key muscle transcription factor, myogenin are increased. Exposure of BC3H-1 cells to a 20-base myogenin antisense oligomer blocked morphological differentiation, and resulted in nearly complete inhibition of the expression of the acetylcholine receptor but not the insulin receptor(IR). In order to study further the relationship between differentiation and IR gene expression, fibroblast growth factor (FGF), a known inhibitor of myogenic differentiation, was employed. FGF treatment inhibited the transcription of both myogenin and the acetylcholine receptor. However FGF did not inhibit the transcription of the IR. These studies indicate therefore that IR transcription increases during muscle cell differentiation, and suggest that during differentiation the control of IR gene expression differs from the control of muscle specific proteins.
Mol Endocrinol 1990 Jun
PMID:Differential effects of fibroblast growth factor on insulin receptor and muscle specific protein gene expression in BC3H-1 myocytes. 217 94

The recent demonstration of estrogen receptors in bone derived cells has stimulated the study of direct effects of sex steroids on bone. We have shown direct stimulation of proliferation by 17 beta-estradiol (E2) of ROS 17/2.8 rat osteogenic osteosarcoma cells, and other bone-derived cells in culture, as well as sex-specific stimulation of diaphyseal bone in vivo by estrogen and testosterone, using [3H]thymidine incorporation into DNA and stimulation of the specific activity of creatine kinase as markers. ROS 17/2.8 cells were used as models of osteoblast-like cells to study the reciprocal modulation of stimulation of bone cell proliferation by sequential treatment by sex steroid and calciotrophic hormones. Pretreatment with 1,25(OH)2D3 and PTH augmented stimulation by E2, while pretreatment with PGE2 followed by E2 resulted in no additional stimulation. Reciprocally, pretreatment with E2 significantly reduced the response to PGE2 while showing an insignificant effect on the response to the other hormones. Gonadectomized Wistar-derived rats provided a useful model system for study of postmenopausal osteoporosis. In diaphyseal bone, [3H]thymidine incorporation and creatine kinase activity decreased 4 weeks after gonadectomy. At that time, a single i.p. injection of E2 in females, and testosterone in males, resulted in a highly significant increase in both these parameters within 24 h.
J Steroid Biochem Mol Biol 1990 Nov 20
PMID:Hormonal stimulation of bone cell proliferation. 225 46

Crystals of mitochondrial creatine kinase isolated from chicken heart were grown by precipitation with polyethylene glycol 1000. The enzyme has been crystallized in the absence and presence of ATP in two different space groups. Crystals are tetragonal, with space group P42(1)2, a = b = 171 A, c = 150 A in the absence of ATP; and P422, a = b = 101 A, c = 114.4 A in the presence of ATP. We suggest that there is one octamer (346 kDa) per asymmetric unit without ATP and one dimer (86 kDa) per asymmetric unit with ATP. Using synchrotron radiation, the octameric form diffracts to at least 3 A resolution.
J Mol Biol 1990 Dec 20
PMID:Crystallization and preliminary X-ray analysis of two different forms of mitochondrial creatine kinase from chicken cardiac muscle. 226 58

We have demonstrated previously that 17 beta-estradiol (E2) stimulates cell proliferation in skeletal tissues, as measured by increased DNA synthesis and creatine kinase (CK) specific activity, and that calciotrophic hormones modulate E2 activity in rat osteoblastic sarcoma cells (ROS 17/2.8). Moreover, E2 failed to stimulate DNA synthesis in vitamin D-depleted female rat bone in the absence of prior i.p. injections of 1.25(OH)2D3. We have, therefore, studied the effects of pretreatment of cells by one hormone on their response to challenge by a second hormone. We now report reciprocal interactions of sex steroids and other hormones modulating bone formation on cell proliferation parameters in primary bone and cartilage cell cultures: these interactions can selectively augment or diminish cell responsiveness to a given hormone. Pretreatment of rat epiphyseal cartilage cell cultures with 1.25(OH)2D3, 24.25(OH)2D3 or parathyroid hormone (PTH) for 5 days, followed by E2 treatment for 24h, resulted in increased DNA synthesis compared to cultures pretreated with vehicle. Prostaglandin (PGE2) pretreatment blocked further response to E2. In the reciprocal case, rat epiphyseal cartilage cells, pretreated with E2, showed an increased response to PTH, a loss of the response to PGE2 or 24.25(OH)2D3 and an inhibition of CK activity and DNA synthesis by 1.25(OH)2D3, similar to the characteristic inhibitory action of 1.25(OH)2D3 in osteoblasts. By contrast, rat epiphyseal cartilage cells pretreated with testosterone showed no changes in response to PTH, 24.25(OH)2D3 or PGE2 and a decreased response to E2, but were stimulated by 1.25(OH)2D3. Rat embryo calvaria cell cultures behaved similarly to epiphyseal cartilage cultures except that 24.25(OH)2D3 pretreatment did not increase the response to E2. Reciprocally, pretreatment with E2 before exposure to calciotrophic hormones did not change the responses of rat embryo calvaria cell cultures to 1.25(OH)2D3 or 24.25(OH)2D3. These findings suggest that the mutual interactions between calciotrophic hormones and E2, demonstrated here in vitro, could selectively affect the responses of bone and cartilage cells to E2 by several mechanisms. These possibilities include increased E2 receptors and E2-stimulated differentiation of cartilage cells to more E2 responsive cells showing some characteristics of osteoblasts.
J Steroid Biochem Mol Biol 1990 Nov 30
PMID:Reciprocal modulation by sex steroid and calciotrophic hormones of skeletal cell proliferation. 227 32


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