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)

Down syndrome candidate region 1 (DSCR1; also known as RCAN1 or Adapt78) has been shown to be induced by calcium overload and oxidative stress which are included in the pathogenic hallmarks of the ischemic diseases. After ischemic stroke, inflammatory responses play an important role in the exacerbation of neuronal loss. In this study, we investigated the expression pattern of DSCR1 in the mouse cortex after transient middle cerebral artery occlusion (MCAO). Then, in vitro studies were taken to address whether inflammatory mediators could induce DSCR1. Male C57BL/6 mice were subjected to transient MCAO for 35 min and sacrificed at 6, 24, and 72 h after the reperfusion. The expression of DSCR1 began to increase in layer VI of the peri-infarct cortex at 24 h and was prominently enhanced at 72h after transient MCAO. Moreover, real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry showed that the induction of the DSCR1 isoform 4 (DSCR1-4) mRNA preceded the expression of the DSCR1 protein. In in vitro studies, tumor necrosis factor alpha and interleukin-1beta (IL-1beta) were found to induce strong upregulation of DSCR1-4 mRNA. Furthermore, western blot analysis revealed that overexpression of DSCR1-4 in SK-N-SH neuroblastoma cells attenuated IL-1beta-induced cyclooxygenase 2 and intercellular adhesion molecule 1 expression. These results demonstrate upregulation of DSCR1 in the mouse peri-infarct cortex following transient MCAO. In addition, our results suggest that inflammatory mediators such as TNFalpha and IL-1beta can induce DSCR1-4 transcription, which may be associated with the alleviation of inflammatory processes.
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PMID:Upregulation of DSCR1 (RCAN1 or Adapt78) in the peri-infarct cortex after experimental stroke. 1848 47

In the present study, we observed the expression of toll-like receptor 4 (TLR4) and its downstream signal pathway in peripheral blood monocytes (PBMs) from patients with acute cerebral infarct (ACI). The expression of TLR4 and MyD88 by PBMs was determined by flow cytometry and reverse transcriptase-polymerase chain reaction, and nuclear factor-kappaB (NF-kappaB) activity was detected by electrophoretic mobility shift assay. Ischemia/reperfusion injury-induced cerebral edema, infarction area, and neurologic impairment scores were determined in MyD88 gene knockout mice. The results indicated a significant increase in circulating TLR4(+) monocytes in ACI patients as compared with the control group and the transient ischemia attack (TIA) group. This change paralleled an elevation in TLR4mRNA transcription and serum tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 in the ACI and TIA groups. Correlation analysis showed TLR4 expression to significantly correlate with cytokine levels and stroke severity. MyD88mRNA differed insignificantly among the three groups. Compared with wild-type mice, 6 h of cerebral ischemia followed by 24 h of reperfusion did not significantly change cerebral edema, cerebral infarction area, and neurologic impairment scores in MyD88 gene knockout mice. Compared with the control group, serum heat shock protein (HSP) 60 increased significantly in the ACI and TIA groups, leading to NF-kappaB activation in TLR4/CD14-transfected HEK293 cells. It is suggested that upregulated TLR4 expression on PMBs may act as one of the peripheral mechanisms of inflammatory injury after ACI. Moreover, circulating HSP60 may be a ligand for TLR4, which is involved in the peripheral mechanism of inflammatory injury after ACI, possibly through an MyD88-independent signal pathway.
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PMID:Upregulated expression of toll-like receptor 4 in monocytes correlates with severity of acute cerebral infarction. 1852 39

We previously reported that the blood-brain barrier (BBB) function was deteriorated in vessels located in the hippocampus, but not the cerebral cortex, in 3-month-old stroke-prone spontaneously hypertensive rats (SHRSP). Recently published data suggest that matrix metalloproteinase (MMP)-2 and MMP-9 play a critical role in the BBB disruption in stroke or cerebral ischemia. In this study, we examined gene and protein expressions of MMPs in the BBB-damaged hippocampal vessels of 3-month-old SHRSP, in the cerebral cortical vessels without BBB damage of SHRSP, and in the hippocampal and cerebral cortical ones without BBB damage of 3-month-old Wistar Kyoto (WKY) rats. The expressions of MMPs were examined by real-time quantitative reverse transcriptase-PCR (RT-PCR), western blotting and immunohistochemical techniques. The gene and protein expressions of MMP-13 were significantly increased in the hippocampal samples of SHRSP compared with samples without BBB damage, such as cerebral cortical samples of SHRSP or hippocampal samples of WKY. Immunostaining of MMP-13 was seen in the cytoplasm of ED-1-positive perivascular cells in both rats and was colocalized with those of type IV collagen or osteopontin. The type IV collagen was also localized in the basement membrane. These findings indicate that the expression of MMP-13 is increased in BBB-damaged hippocampal vessels in hypertensive SHRSP compared with vessels without BBB impairment in normotensive WKY rats and may be involved in vascular remodeling.
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PMID:The expression of matrix metalloproteinase-13 is increased in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model. 1930 Apr 51

Microglial cells are the prime effectors in immune and inflammatory responses of the central nervous system (CNS). During pathological conditions, the activation of these cells helps restore CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory molecules and neurotoxins. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target stroke and neurodegenerative diseases. Chunghyuldan, a combinatorial drug consisting of Scutellariae Radix, Coptidis Rhizoma, Phellodendri Cortex, Gardeniae Fructus, and Rhei Rhizoma, has an inhibitory effect on stroke recurrence in patients with small-vessel disease. It has also been reported to confer antihypertensive, antihyperlipidemic, and antiinflammatory effects. The aim of this study was to examine whether Chunghyuldan suppresses microglial activation. Chunghyuldan was effective at inhibiting LPS-induced nitric oxide (NO) release from rat brain microglia. Real-time reverse transcriptase PCR analysis revealed that pretreatment of rat brain microglia with Chunghyuldan attenuated the LPS-induced expression of mRNAs encoding inducible NO synthase, tumor necrosis factor (TNF)-alpha, interleukin-1beta, and cyclooxygenase-2. In rat brain microglia, Chunghyuldan reduced the LPS-stimulated production of TNF-alpha and prostaglandin E2. In addition, Chunghyuldan significantly decreased LPS-induced phosphorylation of the ERK1/2 and p38 signaling proteins. These results suggest that Chunghyuldan provide neuroprotection by reducing the release of various proinflammatory molecules from activated microglia.
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PMID:Chunghyuldan attenuates brain microglial inflammatory response. 1952 39

Differential renal expression of a homolog of the angiotensin-converting enzyme (ACE), that is, ACE2, has been implicated as a genetic basis of polygenetic hypertension in the stroke-prone spontaneously hypertensive rat model. However, data on the role of ACE2 in hypertension are still inconclusive. Therefore, we analyzed kidney ACE2 mRNA, ACE2 protein and ACE2 enzyme activities in the adult polygenetic stroke-prone spontaneously hypertensive rat (SHRSP) and the monogenetic TGR(mREN2)27 rat models, in comparison with their normotensive reference strains, Wistar-Kyoto (WKY) and Spraque-Dawley (SD) rats, respectively. Kidney ACE2 mRNA was studied using quantitative real-time reverse transcriptase-PCR (RT-PCR) in cortex and medulla, whereas protein expression was scored semiquantitatively in detail in different renal structures using immunohistochemistry. Furthermore, total renal tissue ACE2 activity was measured using a fluorimetric assay that was specified by the ACE2 inhibitor DX600. In SHRSP and homozygous TGR(mREN2)27 rats with established hypertension, kidney ACE2 mRNA, protein and tissue ACE2 activities were not different from their respective WKY and SD reference strain, respectively. In addition, when we looked at renal localization, we found ACE2 protein to be predominantly present in glomeruli and endothelium with weak staining in distal and negative staining in proximal tubuli. Thus, our data challenge previous work that implicates ACE2 as a candidate gene for hypertension in SHRSP by reporting a significant reduction of ACE2 in the kidneys of SHRSP. Taken together, renal ACE2 is not altered in the SHRSP and TGR(mREN2)27 genetic rat models with established hypertension.
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PMID:Renal ACE2 expression and activity is unaltered during established hypertension in adult SHRSP and TGR(mREN2)27. 2001 4

ESCs (embryonic stem cells) are potentially able to replace damaged cells in animal models of neural pathologies such as Parkinson's disease, stroke and spinal cord lesions. Nevertheless, many issues remain unsolved regarding optimal culturing procedures for these cells. For instance, on their path to differentiation in vitro, which usually involves the formation of EBs (embryoid bodies), they may present chromosomal instability, loss of pluripotency or simply die. Therefore, finding strategies to increase the survival of cells within EBs is of great interest. Cannabinoid receptors have many roles in the physiology of the adult body, but little is known about their role in the biology of ESCs. Herein, we investigated how two cannabinoid receptors, CB1 and CB2, may affect the outcome of ESCs aggregated as EBs. RT-PCR (reverse transcriptase-PCR) revealed that EBs expressed both CB1 and CB2 receptors. Aggregation of ESCs into EBs followed by 2-day incubation with a CB1/CB2 agonist reduced cell death by approximately 45%, which was reversed by a CB1 antagonist. A specific CB2 agonist also reduced cell death by approximately 20%. These data indicate that both cannabinoid receptors, CB1 and CB2, are involved in reducing cell death in EBs mediated by exogenous cannabinoids. No increase in proliferation, neural differentiation or changes in chromosomal stability was observed. This study indicates that cannabinoid signalling is functionally implicated in the biology of differentiating ESCs, being the first to show that activation of cannabinoid receptors is able to increase cell viability via reduction of cell death rate in EBs.
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PMID:Cannabinoids modulate cell survival in embryoid bodies. 1994 26

P-glycoprotein, the gene product of ATP-binding cassette, sub-family B (Abcb1), is a representative efflux transporter of cerebral vessels. It was recently reported that the expressions of P-glycoprotein and Abcb1 gene were increased in hippocampal vessels with blood-brain barrier (BBB) damage in stroke-prone hypertensive rats. SAMP8, senescence-accelerated mice with age-related deficits in memory and learning, are known to show age-related damage of BBB. Accordingly, in this study, we examined the P-glycoprotein expression and the gene expression (Abcb1a/b) by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical techniques. SAMR1, which has a spontaneous retroviral insertional mutation in Abcb1a gene, was used to assess the effects of Abcb1a gene mutation. The brain samples of SAMR1 showed decreased expressions of P-glycoprotein and Abcb1a genes and increased expression of Abcb1b gene, compared with those of SAMP8 mice. The P-glycoprotein expression increased with aging in the brain samples of SAMP8, but not in those of SAMR1. The gene expressions of Abcb1a and Abcb1b increased with aging in the brain samples of SAMP8. Immunosignals of P-glycoprotein were seen in vessel walls, mainly in the cytoplasm of CD34-positive endothelial cells and partially in astrocytes, in all mice. These findings indicate that the expressions of Abcb1a and Abcb1b genes and their gene products, P-glycoprotein, were increased with aging in SAMP8, suggesting age-related response to prevent toxic substance from accumulating in the brains of SAMP8.
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PMID:Age-related changes in P-glycoprotein expression in senescence-accelerated mouse. 2002 12

Acid-sensing ion channels (ASICs) are cationic channels that are activated by extracellular acidification and implicated in pain perception, ischemic stroke, mechanosensation, learning, and memory. It has been shown that ASIC1a is an extracellular pH sensor in the central and peripheral nervous systems, but its physiological and pathological roles in non-neural cells are poorly understood. We demonstrated a novel physiological function of ASIC1a in rat articular chondrocytes. The expression of ASIC1a mRNA and protein in rat articular chondrocytes was evaluated by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. The distribution of ASIC1a protein located in articular chondrocytes was determined by using immunofluorescence cell staining. The possible molecular mechanisms of articular chondrocytes pH sensing, as assessed by recording intracellular calcium ([Ca(2+)]i) in chondrocytes, were analyzed by using the laser scanning confocal microscopy technique. The cell injury following acid exposure was analyzed with lactate dehydrogenase release assay and electron microscopy. mRNA and protein expression showed that ASIC1a was expressed abundantly in these cells. In cultured chondrocytes, extracellular pH 6.0 increased intracellular calcium in the presence of extracellular Ca(2+). The ASIC1a-specific blocker PcTX venom significantly reduced this increase in [Ca(2+)]i, and inhibited acid-induced articular chondrocyte injury. However, the increase in [Ca(2+)]i and articular chondrocyte injury were not observed in the absence of extracellular Ca(2+). These findings show that increased [Ca(2+)]i, mediated via ASIC1a, might contribute to acidosis-induced articular chondrocyte injury.
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PMID:Acid-sensing ion channel 1a mediates acid-induced increases in intracellular calcium in rat articular chondrocytes. 2017 94

Advancing age remains the largest risk factor for devastating diseases, such as heart disease, stroke, and cancer. The mechanisms by which advancing age predisposes to disease are now beginning to unfold, due in part, to genetic and environmental manipulations of longevity in lower organisms. Converging lines of evidence suggest that DNA damage may be a final common pathway linking several proposed mechanisms of aging. The present review forwards a theory for an additional aging pathway that involves modes of inherent genetic instability. Long interspersed nuclear elements (LINEs) are endogenous non-LTR retrotransposons that compose about 20% of the human genome. The LINE-1 (L1) gene products, ORF1p and ORF2p, possess mRNA binding, endonuclease, and reverse transcriptase activity that enable retrotransposition. While principally active only during embryogenesis, L1 transcripts are detected in adult somatic cells under certain conditions. The present hypothesis proposes that L1s act as an 'endogenous clock', slowly eroding genomic integrity by competing with the organism's double-strand break repair mechanism. Thus, while L1s are an accepted mechanism of genetic variation fueling evolution, it is proposed that longevity is negatively impacted by somatic L1 activity. The theory predicts testable hypotheses about the relationship between L1 activity, DNA repair, healthy aging, and longevity.
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PMID:A LINE-1 component to human aging: do LINE elements exact a longevity cost for evolutionary advantage? 2034 65

We previously reported that the blood-brain barrier (BBB) function was deteriorated in vessels located in the hippocampus in stroke-prone spontaneously hypertensive rats (SHRSP). In order to assess whether substances with oxidative stress such as amyloid-beta (Abeta) can be scavenged in the BBB-damaged vessels, we examined the gene expression of representative efflux and influx transporters of Abeta, such as low-density lipoprotein receptor (LDLR), LDL-related protein 1 (LRP1), and the receptor for advanced glycation end product (RAGE) in the hippocampus of SHRSP with the BBB impairment and Wistar Kyoto rats (WKY) without the impairment. Real-time quantitative reverse transcriptase-polymerase chain reaction analysis revealed that LDLR gene expression was increased in the samples of SHRSP compared with those of WKY, while there was no significant difference in LRP1 or RAGE gene expression between SHRSP and WKY. Western blot analysis revealed that the protein expression of LDLR was increased in the samples of SHRSP compared with those of WKY. Immunoelectron microscopic examination revealed that the LDLR expression was seen in the luminal and abluminal cytoplasmic membranes and vesicular structures of the endothelial cells and the cytoplasm of perivascular cells, especially in vessels with immunoreactivity of albumin showing increased vascular permeability. These findings suggest that the expression of LDLR was increased in the hippocampus of SHRSP compared with that of WKY and was seen in the luminal and abluminal cytoplasmic membranes and vesicular structures of endothelial cells, suggesting a role of LDLR in the vessels with BBB impairment.
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PMID:The expression of LDL receptor in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model. 2045 92


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