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)

Nitric oxide synthase (NOS) containing nerve regeneration can be seen six months after unilateral cavernous nerve neurotomy in rats. However, its molecular mechanism is still unknown. It is believed that growth factors are involved in this phenomenon. In this study we investigated the change of NOS containing nerve fibers and the RNA expression of insulin like growth factor (IGF)-I, nerve growth factor (NGF), transforming growth factor (TGF)-alpha, TGF-beta 1, TGF-beta 2. TGF-beta 3 and NOS on the penis after cavernous nerve neurotomy in rats. Male rats were divided into three groups: (1) sham operation (N = 10); (2) unilateral neurotomy of a 5 mm segment of the cavernous nerve (N = 15); and (3) bilateral neurotomy (n = 15). Electrostimulation of the intact cavernous nerve or pelvic ganglion was performed at one, three and six months. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining was used to identify NOS in the penile nerve fibers. The gene expression for growth factors and bNOS was investigated in corporal tissue by reverse transcriptase-polymerase chain reaction (RT-PCR) using specific oligonucleotide primers. One month after neurotomy, both unilateral and bilateral neurotomy groups showed a significant decrease in NOS-containing nerve fibers on the dorsal and intracavernosal nerves on the side of neurotomy, and a significantly lower mRNA expression of bNOS, IGF-I and TGF-beta 2. At three months, the number of NOS-containing nerve fibers in the unilateral neurotomy group increased only slightly but at six months those in the intracavernosal nerve increased in a significant amount (P < 0.0001), however mRNA expression of bNOS, IGF-I and TGF-beta 2 showed a significant increase as early as at three months. After bilateral neurotomy, the NOS-positive nerve fibers in the dorsal and intracavernosal nerve were significantly decreased at one month and remained so at six months; no erectile response could be elicited by pelvic ganglion stimulation. In the unilateral neurotomy group at six months, more NOS-positive neurons in the pelvic ganglia were found on the intact side than on the side of the neurotomy (P < 0.003), indicating that the regeneration derives from pelvic ganglion neurons on the intact side. Furthermore, electrostimulation in the unilateral neurotomy group revealed a greater maximal intracavernosal pressure and a shorter latency period at six months than at one month (P < 0.014, P < 0.001, respectively). These data suggest that IGF-I and TGF-beta 2 may play a key role in regeneration of NOS-containing nerve fibers in the dorsal and intracavernosal nerves after unilateral cavernous nerve injury.
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PMID:The role of growth factor on regeneration of nitric oxide synthase (NOS)--containing nerves after cavernous neurotomy in the rats. 1046 23

The insulin-like growth factors (IGFs) are important in the regulation of normal fetal musculoskeletal growth and development, and their actions have been shown to be modulated by IGF binding proteins (IGFBPs). Because the anatomical distribution of IGFBPs is likely to dictate IGF bioavailability, we determined the cellular distribution and expression of IGF-I, IGF-II, and IGFBP-1 to IGFBP-6 in epiphyseal growth plates of the fetal sheep, using immunocytochemistry and in situ hybridization. Little mRNA for IGF-I was detectable within the growth plates, but mRNA for IGF-II was abundant in germinal and proliferative chondrocytes, although absent from some differentiating chondrocytes and hypertrophic cells. Immunohistochemistry for IGF-I and IGF-II showed a presence of both peptides in all chondrocyte zones, including hypertrophic cells. Immunoreactive IGFBP-2 to -5 were localized within the germinal and proliferative zones of chondrocytes, but little immunoreactivity was present within the columns of differentiating cells. IGFBP immunoreactivity again appeared in hypertrophic chondrocytes. IGFBP mRNA in chondrocytes of the epiphyseal growth plate was below the detectable limit of in situ hybridization. However, low levels of mRNAs for IGFBP-2 to -6 were detected by the reverse transcriptase polymerase chain reaction. A co-localization of IGFBPs with IGF peptides in intact cartilage suggests that they may regulate IGF bioavailability and action locally. To test this hypothesis, monolayer cultures of chondrocytes were established from the proliferative zone of the growth plate, and were found to release immunoreactive IGF-II and to express mRNAs encoding IGFBP-2 to -6. Exogenous IGFBP-3, -4, and -5 had an inhibitory action on IGF-II-dependent DNA synthesis. IGFBP-2 had a biphasic effect, potentiating IGF-II action at low concentrations but inhibiting DNA synthesis at equimolar or greater concentrations relative to IGF-II. Long R3 IGF-I, which has a reduced binding affinity for many IGFBPs, was more potent than native IGF-I in promoting DNA synthesis by chondrocytes. Our findings suggest that locally produced IGF-II and IGF-I derived from the circulation can influence fetal epiphyseal chondrogenesis, and that this may be modulated locally by multiple IGFBP expression.
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PMID:Cellular localization and expression of insulin-like growth factors (IGFs) and IGF binding proteins within the epiphyseal growth plate of the ovine fetus: possible functional implications. 1053 72

The molecular mechanism of nitric oxide synthase (NOS)-containing nerve regeneration is still unknown. It is believed that growth factors are involved in this phenomenon. We investigated the change of NOS containing nerve fibers and the mRNA expression of insulin like growth factor (IGF)-I, nerve growth factor (NGF), transforming growth factor (TGF)-alpha, TGF-beta1, TGF-beta2, TGF-beta3, vascular endothelial growth factor (VEGF), endothelial NOS (eNOS) and neuronal NOS (nNOS) on the penis after cavernous nerve neurotomy in rats. Male rats were divided into four groups: (1) sham operation (n = 14); (2) unilateral neurotomy of a 5 mm segment of the cavernous nerve (n = 21); (3) unilateral neurotomy with growth hormone (n = 14); and (4) bilateral neurotomy (n = 21). Electrostimulation of the intact cavernous nerve or pelvic ganglion were performed at one, three and six months. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining and immunohistochemistry were used to identify NOS in the penis. The gene expression for growth factors, eNOS and nNOS were investigated in corporal tissue by reverse transcriptase-polymerase chain reaction (RT-PCR). One month after neurotomy, both unilateral and bilateral neurotomy groups showed significant decreases in NOS-containing nerve fibers on the dorsal and intracavernosal nerves on the side of neurotomy. Significantly lower mRNA expression of nNOS, IGF-I and TGF-beta2, higher mRNA expression of eNOS and VEGF189 were shown in these groups. At three months, the number of NOS-containing nerve fibers in the unilateral neurotomy group increased only slightly, while the GH-treated group showed a significant increase. At six months, those in the intracavernosal nerve only increased in a significant amount (P < 0.0001), however mRNA expression of nNOS, IGF-I and TGF-beta2 showed a significant increase as early as at three months. After bilateral neurotomy, the NOS-positive nerve fibers in the dorsal and intracavernosal nerve were significantly decreased at one month and remained so at six months; no erectile response could be elicited by pelvic ganglion stimulation. In the unilateral neurotomy group at six months, more NOS-positive neurons in the pelvic ganglia were found on the intact side than on the side of the neurotomy (P < 0.003), indicating that the regeneration derived from pelvic ganglion neurons on the intact side. Furthermore, electrostimulation in the unilateral neurotomy group revealed a greater maximal intracavernosal pressure and a shorter latency period at six months than at one month (P < 0.014, P < 0.001, respectively). These data suggest that IGF-I and TGF-beta2 may play a key role in the regeneration of nNOS-containing nerve fibers in the dorsal and intracavernosal nerves, and eNOS increases temporarily in the intracavernous involving VEGF189 after unilateral cavernous nerve injury.
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PMID:IGF-I and TGF-beta2 have a key role on regeneration of nitric oxide synthase (NOS)-containing nerves after cavernous neurotomy in rats. 1055 3

Insulin-like growth factors (IGFs) are expressed in defined spatiotemporal patterns during the development of the mammalian central nervous system (CNS). Since IGF expression in avian species is less well documented, we studied here the expression of IGF-I and IGF-II during chicken CNS development, using in situ hybridization and reverse transcriptase-PCR, and compared the results with the expression of the IGF type 1 receptor (IGF-1R). IGF-II expression started early in embryonic life, shortly after the onset of IGF-1R expression. During organogenesis, IGF-II was strongly expressed in kidney, liver and gut primordia, in contrast with IGF-1R mRNA, which is highly enriched in proliferating neuroepithelia. During the second half of embryonic development, IGF-I and IGF-II had distinct expression patterns, suggesting specific roles for each ligand during brain maturation. IGF-II mRNA was found in numerous brainstem nuclei and in the optic tectum, whereas IGF-I mRNA was found predominantly in telencephalic regions. Both ligands were expressed in the cerebellum, but each by different cell layers. Some brain regions (olfactory bulb and olivo-cerebellar system) did not exhibit the postnatal downregulation typical of extrahepatic IGF-I expression, but continued to express IGF-I into adulthood. Purkinje cells expressed IGF-II in the embryo, but switched to IGF-I expression in the adult. The conservation of embryonic and postnatal IGF expression patterns in the CNS between avians and mammals suggests that the involvement of the IGF system in neurogenesis and differentiation, and possibly in neural plasticity and learning, may have arisen early during tetrapode/vertebrate evolution.
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PMID:Expression of insulin-like growth factor-I (IGF-I) and IGF-II in the avian brain: relationship of in situ hybridization patterns with IGF type 1 receptor expression. 1070 8

IGFs regulate gonadotrophin-stimulated proliferation and differentiation of granulosa and theca cells in vitro. However, the detailed pattern of mRNA expression of IGFs in bovine follicles remains controversial. The objectives of this study were therefore to describe the temporal and spatial pattern of expression of mRNA encoding IGF-I, IGF-II and the type 1 IGF receptor in bovine follicles in vivo. The expression of mRNA encoding IGF-II was detected in theca tissue from around the time of antrum formation up to and during the development of dominance. No IGF-II mRNA expression was detected in granulosa cells. In the majority of follicles we were unable to detect mRNA encoding IGF-I in either granulosa or theca tissue from follicles at any stage of development. Occasionally low amounts of mRNA encoding IGF-I were detected in the theca externa and connective tissue surrounding some follicles. Type 1 IGF receptor mRNA was detected in both granulosa and theca cells of preantral and antral follicles. Expression was greater in granulosa tissue compared with theca tissue. We also measured IGF-I and -II mRNA in total RNA isolated from cultured granulosa and theca cells using reverse transcriptase PCR. In contrast to the in vivo results, IGF-II mRNA was detected in both granulosa and theca tissue. IGF-I mRNA was detected in theca tissue and in very low amounts in granulosa cells. Using a specific IGF-I RIA we were unable to detect IGF-I immunoreactivity in granulosa conditioned cell culture media. Using immunohistochemistry we detected IGF-I immunoreactivity in some blood vessels within the ovarian stroma. We conclude from these results that IGF-II is the principal intrafollicular IGF ligand regulating the growth of bovine antral follicles. In preantral follicles the expression of mRNA encoding type 1 IGF receptor but absence of endogenous IGF-I or -II mRNA expression, highlights a probable endocrine mechanism for the IGF regulation of preantral follicle growth.
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PMID:Expression of mRNA encoding IGF-I, IGF-II and type 1 IGF receptor in bovine ovarian follicles. 1075 40

In spite of the importance of IGF-I for growth and development, knowledge about regulation of its production in submammalian species is rather limited. In order to create a tool for investigation of direct regulatory effects on the expression of IGF-I in bony fish liver, a primary cell culture of hepatocytes from Oreochromis mossambicus, the tilapia, was established. The cells were viable for up to 3 days and IGF-I mRNA synthesis was detected by northern blot and semiquantitative reverse transcriptase (RT)-PCR. Northern blot analysis of the primary cultured hepatocytes revealed four different IGF-I transcripts, 0.5, 1.9, 3.9 and 6.0 kb in size, which were identical to those in liver tissue. However, the expression rate was weaker than that in liver. The direct effects of recombinant tilapia (rt) growth hormone (GH) and salmon (s) IGF-I on the expression of IGF-I in primary cultured hepatocytes were investigated in time-course and dose-response experiments. In untreated cultures, IGF-I mRNA decreased with time. Hepatocytes treated with 100 nM rtGH resulted in a pronounced stimulation of IGF-I mRNA expression throughout the experiment. Treatment with rtGH in concentrations ranging from 0.1 nM to 1 microM caused a clear dose-dependent increase in the amount of IGF-I mRNA. Significant stimulation was obtained even with 0.1 nM, reaching a plateau with 10 nM. Neither significant inhibitory nor stimulatory effects were detected by adding sIGF-I from 0.1 nM to 1 microM to the hepataocytes. Our results indicate that the established primary cell culture of tilapia hepatocytes is a useful system in which to study direct effects of potential regulators of bony fish liver cell function.
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PMID:Primary cultured hepatocytes of the bony fish, Oreochromis mossambicus, the tilapia: a valid tool for physiological studies on IGF-I expression in liver. 1092 16

The expression of mRNAs for transforming growth factors (TGF-beta2, myostatin, activin-B, and follistatin), insulin-like growth factors (IGF-I and -II), and fibroblast growth factor (basic, bFGF) was investigated in satellite cells derived from chicken pectoralis major (PM) and biceps femoris (BF) muscles in the stages from initiation of proliferation to fusion. These growth factor gene cDNAs were synthesized by reverse transcriptase polymerase chain reaction (RT-PCR). No myostatin, activin-B, follistatin or bFGF expression was detected in either cell culture at 0 h. TGF-beta2 mRNA level increased at 48 h (P < 0.01) and remained constant through 144 h in both PM and BF satellite cell cultures. The ontogeny of myostatin gene expression with the exception of a sharp increase in BF culture at 72 h (P < 0.01), was nearly identical in both cell cultures. Activin-B mRNA level in PM satellite cells was higher than that in BF satellite cells at 72 h and 120 h (P < 0.01). Follistatin mRNA in PM satellite cells was higher than that in BF satellite cells at 24, 96, and 120 h culture (P < 0.01). No IGF-I gene expression was detected in cell cultures at any time point. IGF-II gene expression in BF satellite cells declined at 96 h (P < 0.01) and remained reduced until 144 h. bFGF mRNA in both satellite cell cultures increased at 24 h (P < 0.05) and remained at this level in BF satellite cells through 144 h.
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PMID:Temporal expression of growth factor genes during myogenesis of satellite cells derived from the biceps femoris and pectoralis major muscles of the chicken. 1114 9

The insulin-like growth factors (IGFs), IGF-I and IGF-II, play important roles in normal growth and differentiation. In recent studies, IGFs have been implicated in tissue repair and regeneration after hypoxicischemic injury. The growth effects of these genes are exerted primarily through IGF-I receptor (IGF-IR). We have earlier shown that picroliv, obtained from the roots of Picrorhiza kurrooa, reduces cellular damage caused by hypoxia in vitro. We have now studied the modulation of IGF-I, IGF-II and IGF-IR in hypoxia and the ability of picroliv to modify their expression in vivo. Male Sprague-Dawley rats, placed in 10% oxygen for 4 days, were sacrificed, and the expression of IGF-I, IGF-II and IGF-IR was determined by immunohistochemistry, in situ hybridization and reverse transcriptase polymerase chain reaction (RT-PCR) in brain, liver and lung. One group of animals was pretreated with picroliv and the other served as control. IGF-I and IGF-IR were expressed in distinct regions of the brain but not in liver or lung. IGF-I was mainly expressed in the hippocampus and cerebellum, whereas IGF-IR expression was also observed in the cortex. A significant reduction in the messenger RNA (mRNA) level of these genes was observed in response to hypoxia. Pretreatment with picroliv not only prevented such downregulation but more importantly resulted in increased levels of IGF-I and IGF-IR. These observations correlated with reduced neuronal cell death observed in these animals. The mRNA of IGF-II was constitutively expressed and was not altered by hypoxia. Modulation of IGF-I and IGF-II expression by picroliv, a novel pharmacological agent, could benefit in similar clinical settings such as myocardial ischemia and certain cerebral injuries.
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PMID:Picroliv modulates the expression of insulin-like growth factor (IGF)-I, IGF-II and IGF-I receptor during hypoxia in rats. 1121 61

Insulin-like growth factor (IGF)-I and -II are potent mitogens and postulated to exert autocrine, and paracrine effects on growth regulation in human gastric cancer. Their mitogenic effects are tightly regulated by the IGF binding proteins (IGFBPs). In this study, we evaluated the mRNA expression of IGF-I, IGF-II and the IGFBPs in a panel of human gastric cancer cell lines, and normal and tumour tissue specimens from patients with gastric cancer by reverse transcriptase-polymerase chain reaction (RT-PCR) and competitive PCR. Conditioned media (CM) of the gastric cancer cell lines were studied for the secretion of the IGFBPs by western ligand blot (WLB) and western immunoblot (WIB). IGF-I and IGF-II were expressed in all of the gastric cancer cell lines, and the normal and tumour tissue specimens. Overexpression of the IGFs, in particular, IGF-II, was observed in the tumour tissues. The expression pattern of IGFBPs was heterogeneous among the gastric cancer cell lines. IGFBP-2 was expressed in all of the gastric cancer cell lines, whereas IGFBP-1 was not detected in any cell lines. IGFBP-4 was expressed in the most of cell lines. IGFBP-3, IGFBP-5 and IGFBP-6 were expressed in approximately 50% of cell lines. In addition, exogenous IGF-I and IGF-II stimulated the proliferation of gastric cancer cells, suggesting the existence of a functional IGF system in gastric cancer. Taken together, our data-suggest that the IGF-IGFBP system may play an important role in the initiation, progression and metastasis of gastric cancer. Further studies are needed to understand the exact role of IGFs and IGFBPs in gastric neoplasia.
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PMID:Expression of the insulin-like growth factors (IGFs) and the IGF-binding proteins (IGFBPs) in human gastric cancer cells. 1167 16

Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were performed to demonstrate whether a correlation exists between insulin-like growth factors (IGFs)-positive regulators of growth-and myostatin, a negative regulator of muscle growth. IGF-I, -II, and IGF-receptor-1 (IGF-R1) mRNA and IGF-II protein expressions were determined in control and myostatin knockout mice tissues. IGF-I gene expressions were similar between control and knockout mice tissues, whereas IGF-II mRNA levels were significantly higher in myostatin knockout mice kidney and soleus muscles than those of control mice (P <.01). IGF-R1 mRNA levels from control mice heart (P <.05) and kidney (P <.01) were significantly higher than in myostatin knockout mice, whereas levels were lower in pectoralis muscle of control mice than knockout mice (P <.01). The strongly IGF-II-positive cells in soleus muscle were more common in myostatin knockout mice and were seen in a few foci in control mice. IGF-II immunoreactivity in both control and myostatin knockout mice kidneys was localized to the epithelium of renal tubules and collecting ducts. Reciprocal changes in the expression of myostatin and IGF-II and IGF-R1 may underlie normal growth of skeletal muscle and other organs in mammals, and the changes in these tissues associated with disease.
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PMID:IGF-I, IGF-II, and IGF-receptor-1 transcript and IGF-II protein expression in myostatin knockout mice tissues. 1211 49


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