Abstract:The energy sensing AMP-activated protein kinase (AMPK) regulates cellular and whole-body energy balance through stimulating catabolic ATP-generating and suppressing anabolic ATP-consuming pathways thereby helping cells survive during energy depletion. The kinase has previously been reported to be either directly or indirectly involved in the regulation of several carriers, channels and pumps of high significance in cellular physiology. Thus AMPK provides a necessary link between cellular energy metabolism and … Show more
“…It led to NF-κB separating from IκB and entering the nucleus, followed by initiating or enhancing the inflammatory genes transcription and promoting expression of inflammatory factors and inflammatory chemokines, such as tumor necrosis factor-α (TNF-α) and Interleukin-12 (IL-12) [35,36]. TAK1 also activated the mitogen-activated protein kinase (MAPK) signaling pathway, which led to the activation of subgroups extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase and C-jun n-terminal kinase (JNK), followed by formation of transcription factor activator protein-1 (AP-1), regulation of IL-1, IL-6 and TNF-α and other inflammatory factors of transcription in the end [37,38]. Consistent with the effects of Phellinus linteus polysaccharides on LPS-stimulated THP-1 cells [39], CSP-1 treatment significantly inhibited ROS generation and led to downregulation of MyD88 mRNA and TRAF-6 mRNA expression in LPS-induced THP-1 cells.…”
In this study, the extraction conditions of the crude polysaccharide from Cereus sinensis were optimized by response surface methodology. The optimum extraction conditions were: a ratio of raw material to water volume of 1:80 (g/mL); an extraction temperature of 72 °C; and an extraction time of 3 h. Then, a purified polysaccharide named Cereus sinensis polysaccharide-1 (CSP-1) was obtained from the crude polysaccharide by the Diethylaminoethyl cellulose-52 (DEAE-52) cellulose chromatography column and Sephadex G-100 column. The molecular weight and monosaccharide composition of CSP-1 was determined through Gel Permeation Chromatography (GPC) and Gas Chromatography–Mass Spectrometer (GS–MS), respectively. The results showed that CSP-1 with an average molecular weight of 56,335 Da was composed of l-(−)-Fucose, d-(+)-Mannose, d-Glucose and mainly possessed 1→2, 1→2, 6, 1→4, and 1→4, 6 of glycosyl linkages. The immunomodulatory activities of CSP-1 were also evaluated using lipopolysaccharide (LPS)-induced human monocytic (THP-1) cells. The results demonstrated that CSP-1 dose-dependently protected against LPS-induced toxicity, and CSP-1 significantly inhibited the Toll-like receptor 4 (TLR-4) mRNA, myeloid differentiation factor 88 (MyD88) mRNA and tumour necrosis factor receptor-associated factor-6 (TRAF-6) mRNA expression of the LPS-induced THP-1 cells, as well as suppressing reactive oxygen species (ROS) generation.
“…It led to NF-κB separating from IκB and entering the nucleus, followed by initiating or enhancing the inflammatory genes transcription and promoting expression of inflammatory factors and inflammatory chemokines, such as tumor necrosis factor-α (TNF-α) and Interleukin-12 (IL-12) [35,36]. TAK1 also activated the mitogen-activated protein kinase (MAPK) signaling pathway, which led to the activation of subgroups extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase and C-jun n-terminal kinase (JNK), followed by formation of transcription factor activator protein-1 (AP-1), regulation of IL-1, IL-6 and TNF-α and other inflammatory factors of transcription in the end [37,38]. Consistent with the effects of Phellinus linteus polysaccharides on LPS-stimulated THP-1 cells [39], CSP-1 treatment significantly inhibited ROS generation and led to downregulation of MyD88 mRNA and TRAF-6 mRNA expression in LPS-induced THP-1 cells.…”
In this study, the extraction conditions of the crude polysaccharide from Cereus sinensis were optimized by response surface methodology. The optimum extraction conditions were: a ratio of raw material to water volume of 1:80 (g/mL); an extraction temperature of 72 °C; and an extraction time of 3 h. Then, a purified polysaccharide named Cereus sinensis polysaccharide-1 (CSP-1) was obtained from the crude polysaccharide by the Diethylaminoethyl cellulose-52 (DEAE-52) cellulose chromatography column and Sephadex G-100 column. The molecular weight and monosaccharide composition of CSP-1 was determined through Gel Permeation Chromatography (GPC) and Gas Chromatography–Mass Spectrometer (GS–MS), respectively. The results showed that CSP-1 with an average molecular weight of 56,335 Da was composed of l-(−)-Fucose, d-(+)-Mannose, d-Glucose and mainly possessed 1→2, 1→2, 6, 1→4, and 1→4, 6 of glycosyl linkages. The immunomodulatory activities of CSP-1 were also evaluated using lipopolysaccharide (LPS)-induced human monocytic (THP-1) cells. The results demonstrated that CSP-1 dose-dependently protected against LPS-induced toxicity, and CSP-1 significantly inhibited the Toll-like receptor 4 (TLR-4) mRNA, myeloid differentiation factor 88 (MyD88) mRNA and tumour necrosis factor receptor-associated factor-6 (TRAF-6) mRNA expression of the LPS-induced THP-1 cells, as well as suppressing reactive oxygen species (ROS) generation.
“…How AMPK regulates ion channels is diverse and tissue/cell type-specific (Andersen & Rasmussen 2012, Dermaku-Sopjani et al 2014). For example, constitutively active AMPK slows the inactivation of voltage-gated sodium channels (Na v 1.3) and shifts the voltage-activation curve toward more hyperpolarized potentials in rat ventricular myocytes (Light et al 2003).…”
AMPK is a cellular energy sensor, which is activated when the intracellular ATP production decreases. The activities of AMPK display circadian rhythms in various organs and tissues, indicating that AMPK is involved in the circadian regulation of cellular metabolism. In vertebrate retina, the circadian clocks regulate many aspects of retinal function and physiology, including light/dark adaption, but whether and how AMPK was involved in the retinal circadian rhythm was not known. We hypothesized that the activation of AMPK (measured as phosphorylated AMPK) in the retina was under circadian control, and AMPK might interact with other intracellular signaling molecules to regulate photoreceptor physiology. We combined ATP assays, Western blots, immunostaining, patch-clamp recordings, and pharmacological treatments to decipher the role of AMPK in the circadian regulation of photoreceptor physiology. We found that the overall retinal ATP content displayed a diurnal rhythm that peaked at early night, which was nearly anti-phase to the diurnal and circadian rhythms of AMPK phosphorylation. AMPK was also involved in the circadian phase-dependent regulation of photoreceptor L-type voltage-gated calcium channels (L-VGCCs), the ion channel essential for sustained neurotransmitter release. The activation of AMPK dampened the L-VGCC currents at night with a corresponding decrease in protein expression of the L-VGCCα1 pore-forming subunit, while inhibition of AMPK increased the L-VGCC current during the day. AMPK appeared to be upstream of extracellular-signal-regulated kinase (ERK) and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) but downstream of adenylyl cyclase in regulating the circadian rhythm of L-VGCCs. Hence, as a cellular energy sensor, AMPK integrates into the cell signaling network to regulate the circadian rhythm of photoreceptor physiology.
We found that in chicken embryonic retina, the activation of AMP-Activated Protein Kinase (AMPK) is under circadian control and anti-phase to the retinal ATP rhythm. While ATP content is higher at night, phosphorylated AMPK (pAMPK) is higher during the day. AMPK appears to be upstream of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), and mammalian target of rapamycin complex 1 (mTORC1) but downstream of adenylyl cyclase in regulating the circadian rhythm of L-VGCCs. Therefore, as a cellular energy sensor, AMPK integrates into the cell signaling network to regulate the circadian rhythm of photoreceptor physiology.
“…Our results showed that Ab production is regulated by the concentrations of glucose in the culture media. As AMPK serves as a metabolic sensor governing the downstream pathways to cope with energy crises (Burkewitz et al 2014;Dermaku-Sopjani et al 2014;Xiao et al 2011), we further examined the role of AMPK in Ab production. Using pharmaceutical agents to manipulate AMPK activities in APP cells grown in media containing different levels of glucose, we found that energy status and AMPK cooperatively affected the production of Ab.…”
Alzheimer's disease (AD) is the most common form of dementia in the elderly. Accumulation of Aβ peptides in the brain has been suggested as the cause of AD (amyloid cascade hypothesis); however, the mechanism for the abnormal accumulation of Aβ in the brains of AD patients remains unclear. A plethora of evidence has emerged to support a link between metabolic disorders and AD. This study was designed to examine the relationship between energy status and Aβ production. Neuro 2a neuroblastoma cells overexpressing human amyloid precursor protein 695 (APP cells) were cultured in media containing different concentrations of glucose and agonist or antagonist of AMP-activated-protein-kinase (AMPK), a metabolic master sensor. The results showed that concentrations of glucose in the culture media were negatively associated with the activation statuses of AMPK in APP cells, but positively correlated with the levels of secreted Aβ. Modulating AMPK activities affected the production of Aβ. If APP cells were cultured in high glucose medium (i.e., AMPK was inactive), stimulation of AMPK activity decreased the production levels of Aβ. On the contrary, if APP cells were incubated in medium containing no glucose (i.e., AMPK was activated), inhibition of AMPK activity largely increased Aβ production. As AMPK activation is a common defect in metabolic abnormalities, our study supports the premise that metabolic disorders may aggravate AD pathogenesis.
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