Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P31749 (AKT)
 22,954 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intervertebral disc (IVD) degeneration suggests a complex process influenced by genetics, lifestyle and biomechanics, which accounts for the development of low back pain (LBP) and lumbar radiculopathy, a major cause of musculoskeletal disability in humans. The family of Akt/PKB kinases is a principal mediator in the signal transduction pathways, which contribute to transcriptional regulation, cell growth, proliferation, apoptosis, and survival ability. The purpose of this study was to evaluate the transcriptional profile of the AKT family genes in human herniated discs and the involvement of the PI3K-Akt signaling pathway in human IVD degeneration. Real-time PCR analysis was used to assess the mRNA expression pattern of the three Akt/PKB isoforms in 63 herniated and 10 control disc specimens. Our results showed a significant positive correlation between AKT1 and AKT3 mRNA in herniated discs suggesting a synergistic action between these isoforms in disc herniation. Interestingly, AKT2 mRNA was up-regulated in patients with acute pain during the first 12 months, indicating that AKT2 transcriptional activation may be associated with acute rather than chronic inflammation and phagocytosis. Finally, Akt1/PKB transcription presented a stepwise activation as disc herniation deteriorated. Our findings provide evidence on the transcriptional activation of the Akt/PKB pathway indicating that it is involved in lumbar disc degeneration. There is need for further studies to elucidate the exact role and down-stream signaling action of Akt/PKB isoforms in the pathogenesis of lumbar disc herniation.
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PMID:Akt/PKB isoforms expression in the human lumbar herniated disc: correlation with clinical and MRI findings. 2159 Apr 31

It is suggested that most cases of low back pain are related to degeneration of intervertebral discs. Disc degeneration is a chronic and progressive disease and the search for effective medical treatments continues. Neurotropin is widely used in Japan and China to treat low back pain and neck-shoulder-arm syndrome. The present study aimed to investigate the effect of Neurotropin on glycosaminoglycan synthesis in nucleus pulposus cells. Cultured human nucleus pulposus cells were treated with Neurotropin every second day for two weeks. Production of glycosaminoglycan was assessed using a dimethyl-methylene blue assay and PicoGreen was used to measure DNA content. Microarray analysis, real-time PCR, and western blotting were performed to assess the biological processes related to Neurotropin-stimulated glycosaminoglycan synthesis. The results showed that the level of glycosaminoglycan normalized to DNA content was significantly upregulated by the addition of Neurotropin. Gene expression profiling showed over two-fold upregulation of 697 genes in response to Neurotropin treatment. Among these genes, ontological analysis suggested significant implication of phosphatidylinositol 3-kinase signaling, and analysis focused on this pathway demonstrated marked upregulation of angiopoietin 1 and insulin-like growth factor 1. Activation of phosphorylation of the signal transducer protein AKT was detected by western blotting. Of the genes related to sulfated glycosaminoglycan synthesis, the greatest increase in mRNA levels was observed for chondroitin sulfate N-acetylgalactosaminyltransferase 1, an enzyme initiating synthesis of chondroitin sulfate side chains attached to a core protein of aggrecan, which is a predominant disc matrix component. These findings suggest that Neurotropin may activate the phosphatidylinositol 3-kinase-AKT pathway and stimulate glycosaminoglycan synthesis through upregulation of expression of mRNA for chondroitin sulfate N-acetylgalactosaminyltransferase 1. Because there was no cytotoxic cellular growth inhibition, Neurotropin treatment might offer an accessible therapeutic strategy for intervertebral disc degeneration.
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PMID:Upregulation of glycosaminoglycan synthesis by Neurotropin in nucleus pulposus cells via stimulation of chondroitin sulfate N-acetylgalactosaminyltransferase 1: A new approach to attenuation of intervertebral disc degeneration. 3014 73

Degenerative disc disease (DDD) is the main cause of low back pain, and the ingrowth of new blood vessels is one of its pathological features. The stromal cell-derived factor 1 (SDF1)/CXCR7 signaling axis plays a role in these physiological and pathological activities. The aims of this study were to explore whether this signaling axis participates in the angiogenesis of degenerated intervertebral discs (IVDs) and to define its underlying mechanism. In this study, we cocultured human nucleus pulposus cells (NPCs) and vascular endothelial cells (VECs) and regulated the expression of SDF1/CXCR7 to investigate the effect of VEC angiogenesis by NPCs. The results revealed that angiogenesis was enhanced with increased SDF1 and that angiogenesis was weakened with the inhibition of CXCR7. We found that PI3K/AKT was involved in the downstream pathway in the coculture. VEC angiogenesis induction by NPCs was enhanced with an increase in pAKT or a decrease in PTEN. We conclude that the SDF1/CXCR7 signaling axis plays a role in the angiogenesis of degenerated IVD through the PI3K/AKT pathway.
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PMID:SDF1/CXCR7 Signaling Axis Participates in Angiogenesis in Degenerated Discs via the PI3K/AKT Pathway. 3086 29

Objectives: Intervertebral disc degeneration (IDD) is widely accepted as a cause of low back pain and related degenerative musculoskeletal disorders. Nucleus pulposus (NP) cell apoptosis which is related to excessive endoplasmic reticulum (ER) stress in the intervertebral disc (IVD) could aggravate IDD progression. Many studies have shown the therapeutic potential of exosomes derived from bone marrow mesenchymal stem cells (MSC-exos) in degenerative diseases. We hypothesized that the delivery of MSC-exos could modulate ER stress and inhibit excessive NP cell apoptosis during IDD. Methods: The ER stress levels were measured in normal or degenerative NP tissues for contrast. The effects of MSC-exos were testified in advanced glycation end products (AGEs) -induced ER stress in human NP cells. The mechanism involving AKT and ERK signaling pathways was investigated using RNA interference or signaling inhibitors. Histological or immunohistochemical analysis and TUNEL staining were used for evaluating MSC-exos therapeutic effects in vivo. Results: The ER stress level and apoptotic rate was elevated in degenerative IVD tissues. MSC-exos could attenuate ER stress-induced apoptosis by activating AKT and ERK signaling. Moreover, delivery of MSC-exos in vivo modulated ER stress-related apoptosis and retarded IDD progression in a rat tail model. Conclusions: These results highlight the therapeutic effects of exosomes in preventing IDD progression. Our work is the first to demonstrate that MSC-exos could modulate ER stress-induced apoptosis during AGEs-associated IVD degeneration.
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PMID:Exosomes from mesenchymal stem cells modulate endoplasmic reticulum stress to protect against nucleus pulposus cell death and ameliorate intervertebral disc degeneration in vivo. 3128 33

Intervertebral disc degeneration (IDD) is recognized as the major contributor to low back pain, which results in disability worldwide and heavy burdens on society and economy. Here we present evidence that the lower level of Nrf2 is closely associated with higher grade of IDD. The apoptosis and senescence of nucleus pulposus cells (NPCs) were exacerbated by Nrf2 knockdown, but suppressed by Nrf2 overexpression under oxidative stress. Based on findings that Kinsenoside could exert multiple pharmacological effects, we found that Kinsenoside rescued the NPC viability under oxidative stress and protected against apoptosis, senescence and mitochondrial dysfunction in a Nrf2-dependent way. Further experiments revealed that Kinsenoside activated a signaling pathway of AKT-ERK1/2-Nrf2 in NPCs. Moreover, in vivo study showed that Kinsenoside ameliorated IDD in a puncture-induced model. Together, the present work suggests that Nrf2 is involved in the pathogenesis of IDD and shows the protective effects as well as the underlying mechanism of Kinsenoside on Nrf2 activation in NPCs.
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PMID:Kinsenoside ameliorates intervertebral disc degeneration through the activation of AKT-ERK1/2-Nrf2 signaling pathway. 3154 35