Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection with the human immunodeficiency virus (HIV) can lead to global alterations in metabolism as well as immunodeficiency. There is dysregulation of endocrine function in adults and children, the extent and magnitude correlating with disease progression. Some of the more prominent abnormalities occur in the thyroid, gonadal, and somatomedin axes. Clinical manifestations of these abnormalities are growth failure in children, which is one of the most sensitive indicators of disease progression, and a wasting syndrome in adults and children. Although there are case reports of growth hormone (GH) deficiency in HIV-infected children, most patients with growth failure have normal serum levels of GH and normal to low levels of insulin-like growth factor-I (IGF-I). Antiretrovial therapy can improve the growth rate in children for a period of time if there is a drop in viral titer, but as the viral load increases, the growth rate decreases again. Administration of GH or IGF-I to these patients can improve the growth rate and lean body mass, and in some patients improve immune function. Although studies on resting energy expenditure in HIV-infected patients have shown increases, these are not proportional to disease progression, but may be dependent upon cytokine activation and other abnormalities. Adult patients with wasting have been shown to have relatively normal total energy expenditure, but decreased intake. Appetite stimulants have been shown to have some benefit, but do not increase lean body mass. The most significant clinical benefit has come from administration of GH in short-term trials. GH and IGF-I are both able to inhibit apoptosis and reconstitute the immune system in rodents treated with ablative therapy. In addition, GH can modulate the marrow suppressive effects of zidovudine and may enhance its ability to inhibit viral reverse transcriptase. Current clinical trials are ongoing in both adults and children. GH and IGF-I may have a role in regimens intended for immune reconstruction, and could be useful as adjuvant therapy in selected patients with HIV infection.
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PMID:Use of human recombinant growth hormone and human recombinant insulin-like growth factor-I in patients with human immunodeficiency virus infection. 895 Jun 24

The expression of insulin receptor substrate-I (IRS-I) mRNA was demonstrated in rat luteal cells by Northern blot analysis, in situ hybridization as well as by reverse transcriptase polymerase chain reaction. Western blot with a polyclonal anti IRS-I antibody showed the presence of a 183 kDa protein which corresponds to the size of IRS-I reported in other tissues. Further studies were performed to determine whether human chorionic gonadotropin (hCG) can interact with the insulin-like growth factor-I (IGF-I) signaling pathway to increase tyrosine phosphorylation of IRS-I. While hCG alone was ineffective in stimulating the phosphorylation of IRS-I, IGF-I mediated phosphorylation of IRS-I was increased by prior exposure to hCG. These results were further confirmed by the immunoprecipitation of IRS-I from the lysate of hCG- and IGF-I-treated luteal cell cultures followed by Western blotting with anti-phosphotyrosine antibody. Similarly, pretreatment with forskolin also increased IGF-I stimulated IRS-I phosphorylation. The increased tyrosine phosphorylation of IRS-I seen in response to IGF-I stimulation following treatment with either hCG or forskolin was not due to an increase in IRS-I content. Furthermore, IGF-I receptor tyrosine kinase activity was not affected by forskolin, suggesting that the increase in IRS-I tyrosine phosphorylation was not the result of an increase in its activity. Thus, we conclude that hCG/LH and IGF-I signaling pathways 'cross-talk' to increase the levels of IRS-I tyrosine phosphorylation. The observed increase in IRS-I tyrosine phosphorylation may be the result of an increase in the stability of the phosphorylated form of IRS-I.
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PMID:IRS-I expression on the luteinized rat ovary: IGF-I and cyclic AMP effects on IRS-I tyrosine phosphorylation. 924 69

Growth hormone (GH) increases the amount of insulin-like growth factor-I (IGF-I) mRNA in rat skeletal muscle, but this effect has not been demonstrated in human muscle. An autocrine effect of IGF-I produced in muscle may be an important determinant of the increased muscle mass associated with GH therapy. Thus, we examined IGF-I mRNA abundance in skeletal muscle biopsy samples taken 10 h after a subcutaneous injection of GH (0.03 mg/kg, n = 6) or placebo (normal saline, n = 5) in men and women over 60 years of age. Relative tissue concentrations of IGF-I mRNA were evaluated with a competitive reverse transcriptase-polymerase chain reaction assay. Mean plasma IGF-I concentrations rose steadily after the GH injection, and were 74% higher in the GH group than in the control group at the time of the muscle biopsies. There was no consistent difference between the GH and control groups in muscle IGF-I mRNA abundance when expressed in relation to total RNA or polyadenylated RNA. However, one GH-treated subject had three times more IGF-I mRNA, relative to polyadenylated RNA, than the average control subject. There was no effect of GH on levels of mRNAs encoding the most abundant myofibrillar proteins, actin and myosin heavy chain. These data do not support the hypothesis that increased IGF-I mRNA abundance in skeletal muscle is required for the anabolic effect of GH in people over 60 years of age.
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PMID:Insulin-like growth factor-I, actin, and myosin heavy chain messenger RNAs in skeletal muscle after an injection of growth hormone in subjects over 60 years old. 939 11

The dysmyelinating mutant jimpy (jp) arises from a point mutation in the mouse gene encoding proteolipid protein and is characterized by severe dysmyelination attributable to oligodendrocyte death. This mutant was used to investigate the regulation of oligodendrocyte progenitor proliferation in the postnatal spinal cord. At postnatal day 18, jp spinal cord contained a three- to eightfold greater number of proliferating oligodendrocyte progenitor cells than did wild-type (wt) spinal cord. Increased proliferation in jp spinal cord was accompanied by a twofold increase in the number of progenitor cells. Semiquantitative reverse transcriptase-PCR revealed no change in the level of mRNA encoding the platelet-derived growth factor A, transforming growth factor-beta, or insulin-like growth factor-I, all of which have been implicated as regulators of proliferation and differentiation of oligodendrocyte progenitor cells. There was, however, a 17-fold increase in the level of mRNA encoding the chemokine GRO-1 and a 5- to 6-fold increase in GRO-1 protein in the jp spinal cord. Double immunofluorescence labeling revealed elevated levels of GRO-1 in reactive astrocytes in jp spinal cord white matter. In vitro studies indicated that extracts from jp spinal cord stimulated oligodendrocyte progenitor proliferation. Furthermore, removal of GRO-1 from jp extracts by immunoprecipitation reduced the proliferation of progenitor cells to a level similar to that achieved by wt extracts. These findings suggest a novel mechanism by which proliferation of oligodendrocyte progenitor cells is regulated in the postnatal spinal cord in response to insult.
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PMID:Elevated levels of the chemokine GRO-1 correlate with elevated oligodendrocyte progenitor proliferation in the jimpy mutant. 1072 41

Cells in normal tendon are in a resting G0 state, performing maintenance functions. However, traumatic injury introduces growth factors such as platelet-derived growth factor and insulin-like growth factor from blood as well as activates endogenous growth factors. These factors stimulate migration and proliferation of tendon cells at the wound area. Tendon cells require growth-promoting factors to transit the cell cycle. To evaluate the contribution of endogenous growth factors in tendon, extracts of the epitenon and internal compartment of avian flexor tendon as well as medium of cultured cells from the epitenon (tendon surface cells) and internal tendon (tendon internal fibroblasts) were collected to assess their ability to stimulate DNA synthesis. Acid-ethanol extracts of tissues and medium were chromatographed on a P-30 molecular sieve column and assayed for mitogenic activity by quantitating [3H]thymidine incorporation into tendon cell DNA. The extract from the internal tendon compartment was more stimulatory for DNA synthesis than that from the epitenon, particularly when tested on tendon internal fibroblasts. However, conditioned medium fractions from surface epitenon cells stimulated DNA synthesis to a high degree on both tendon surface cells and tendon internal fibroblasts. Conditioned medium from tendon internal fibroblasts was also stimulatory. An anti-insulin-like growth factor-I antibody ablated most of the mitogenic activity present in both tissues and conditioned medium. The levels of acid-extractable insulin-like growth factor-I in tendon were determined by competitive radioimmunoassay as 1.48+/-0.05 ng/g tissue for the epitenon and 3.83+/-0.03 ng/g tissue for the internal compartment. Results of Western immunoblots of conditioned medium revealed insulin-like growth factor-I at the 7.5 kDa position. Cultured tendon surface cells and tendon internal fibroblasts as well as cells in intact flexor tendon expressed insulin-like growth factor-I mRNA detected by reverse transcriptase-polymerase chain reaction. In situ hybridization histochemistry positively identified insulin-like growth factor-I mRNA in tendons from 52-day-old chickens. Platelet-derived growth factor was not detected at the protein or message levels. Furthermore, tendon surface cells and tendon internal fibroblasts both expressed receptors for insulin-like growth factor-I detected by flow cytometry. These data suggest that tendon cells express insulin-like growth factor-I mRNA and synthesize insulin-like growth factor-I in both the epitenon and the internal compartment of tendon, which is present in an inactive form, most likely bound to insulin-like growth factor-binding proteins.
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PMID:Insulin-like growth factor-I is expressed by avian flexor tendon cells. 1105 90

The signal initiating ovarian theca cell (TC) differentiation is gonadotropin independent because theca precursor cells do not contain LH receptors. Previously we demonstrated that preantral follicles produce paracrine TC differentiating factors that promote androgen production by an LH-independent mechanism. This study tested the effects of two granulosa cell-produced peptides, insulin-like growth factor-I (IGF-I) and stem cell factor (SCF), on TC differentiation and androgen production. Neutralizing antibodies to either IGF-I or SCF blocked the stimulatory effects of follicle-conditioned medium on TC precursor differentiation more than 90%. The TC isolated from the ovaries of hypophysectomized immature rats by percoll gradient centrifugation were cultured (48 h) with and without SCF (0-100 ng/ml) and IGF-I (0-100 ng/ml) to test their effects on TC differentiation. Androsterone in the medium was measured by RIA. Luteinizing hormone receptor, steroidogenesis acute regulatory protein (StAR), CYP11A, CYP17, and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) mRNAs were measured by specific reverse transcriptase polymerase chain reaction assays. Stem cell factor or IGF-I alone did not stimulate androsterone production but in combination caused a concentration-dependent increase in androsterone levels. Maximum androsterone levels were less than those stimulated by LH (0.1 ng/ml) alone. Although IGF-I synergistically augmented LH stimulation of androsterone production, SCF did not alter LH-stimulated androsterone production in the presence or absence of IGF-I. Stem cell factor alone had no effect on LH receptor, StAR, CYP11A, and 3beta-HSD mRNA expression but decreased CYP17 mRNA levels. Insulin-like growth factor-I alone had no effect on StAR or CYP17 mRNA expression but increased LH receptor, CYP11A, and 3beta-HSD mRNA levels. In combination, SCF plus IGF-I increased the expression of all five mRNAs. These data support the conclusion that IGF-I and SCF are important regulators of TC differentiation.
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PMID:Stem cell factor and insulin-like growth factor-I stimulate luteinizing hormone-independent differentiation of rat ovarian theca cells. 1115 46

We previously demonstrated that the development of cultured rat pre-antral follicles is stimulated by growth hormone (GH) and insulin-like growth factor-I (IGF-I) and that the mRNA of IGF-I and type I IGF receptor (IGFR) is present in the oocyte and wall of these follicles. To gain a closer insight into the regulation of early folliculogenesis by GH and IGF-I, the present study investigated the gene expression of GH and GHR mRNA in isolated oocytes and follicular wall cells of pre-antral follicles, using reverse transcriptase polymerase chain reaction, and the localisation of immunoreactive IGF-I, IGFR, GH and GHR proteins in ovarian sections of 10-day-old rats. GH was detected in oocytes and follicular wall tissue of pre-antral follicles, whereas expression of the GH mRNA was absent. The GHR mRNA was present in follicular wall tissue and not in the oocyte, while positive immunostaining for GHR was observed in all cells of the pre-antral follicles. Immunoreactive IGF-I and IGFR was also visible in the pre-antral follicles, especially in the oocytes. In conclusion, the data show that the previously demonstrated local gene expression of IGF-I and IGFR in oocytes and their enveloping follicular cells also leads to translation, which points to the involvement of intrafollicular IGF-I in early follicular development. The presence of the GHR mRNA and the GHR and GH proteins in pre-antral follicles in the absence of ovarian GH mRNA suggest a direct effect of systemic GH on early follicular development.
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PMID:Immunohistochemical localisation of growth hormone (GH), GH receptor (GHR), insulin-like growth factor I (IGF-I) and type I IGF-I receptor, and gene expression of GH and GHR in rat pre-antral follicles. 1196 96

Whether cultured bovine trabecular meshwork cells and trabecular tissue ex vivo express insulin-like growth factor-I (IGF-I) messenger RNA (mRNA) and protein was investigated. Total RNA of cultured bovine trabecular meshwork cells as well as trabecular meshwork tissue freshly excised from bovine eyes was extracted, and reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect IGF-I mRNA. RT-PCR product was verified by sequencing. Immunohistochemical stain was used to detect IGF-I protein. The results showed that a single PCR amplified product was obtained, and the sequence was homologous to the known sequence.. IGF-I immunostain was positive in the cytoplasm of trabecular meshwork cells. It was concluded that trabecular meshwork cells produce IGF-I and contribute to the presence of IGF-I in trabecular meshwork microenvironment as well as aqueous humor. Trabecular meshwork cells were affected by IGF-I not only through paracrine, but also autocrine action. Whether abnormal down-regulations in IGF-I production may contribute to the pathogenesis of primary open-angle glaucoma and the possibility of promoting the autocrine action of IGF-I by trabecular meshwork cells to treat the disease is worth further investigation.
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PMID:Insulin-like growth factor-I gene cloning and protein expression in bovine trabecular meshwork tissue and cells. 1265 89

In vertebrates insulin-like growth factors (IGFs) regulate important cellular activities involving proliferation, differentiation, and antiapoptosis and their biological activities are mediated through the insulin-like growth factor-I receptor (IGF-IR). To understand the functions of IGF-IR in zebrafish embryogenesis, the polymerase chain reaction (PCR) cloning technique was applied to isolate the IGF-IR gene. A 5'-truncated 3285-nucleotide zebrafish IGF-IR sequence was assembled from 3 overlapping clones. This contained a partial coding region of 1550 nucleotides and a 1735-nucleotide 3' untranslated region. The deduced 515 amino acid residues included the conserved kinase domain and shared 60.9%, 61.1%, and 59.9% homology to human, mouse, and frog, respectively. To understand the relationship of IGF-IR with p53 suppressor gene during embryogenesis, expression of both genes was analyzed in parallel by semicompetitive reverse transcriptase PCR and whole-mount in situ hybridization. This analysis indicated that messenger RNA of both genes was of maternal origin, but the p53 suppressor mRNA was relatively more abundant than the IGF-IR message in most of the developmental stages, except possibly at 28 hours postfertilization. At this stage the IGF-I receptor message was highly expressed and visible in whole internal organ regions by whole-mount in situ hybridization, while p53 message was concentrated in the head portion and barely detectable in the trunk portion. The results suggest that IGF-IR and p53 mRNA are expressed at different places and different times. However, the temporal and spatial relationship of IGF-IR and its relationship to p53 suppressor protein during developmental processes remain unknown.
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PMID:Gene expression of insulin-like growth factor-I receptor and p53 suppressor during zebrafish (Danio rerio) embryogenesis. 1496 Dec 57

The effects of insulin-like growth factor-I (IGF-I) on the ghrelin receptor [growth hormone secretagogue receptor (GHS-R)] gene expression and on the GH response to GHS in rat pituitary cell cultures were examined. Pituitary GHS-R mRNA levels were decreased in a dose (0.01-10 nM)- and time (4-12 h)-dependent manner by IGF-I as measured with reverse transcriptase (RT)-PCR. The basal GH secretion was not influenced by the pretreatment with IGF-I (1 nM for 8 h); however, the GH response to the receptor ligand, a synthetic GHS, KP-102 (100 nM, 15 min), was significantly reduced by pretreatment with IGF-I. Thus, the present studies indicate that IGF-I could inhibit GH secretion at least in part by regulating the expression of the GHS-R.
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PMID:Insulin-like growth factor-I down-regulates ghrelin receptor (growth hormone secretagogue receptor) expression in the rat pituitary. 1568 Apr 88


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