|
| ||
|
|
||
Cellular ATP Levels (cellular + atp_level)
Selected AbstractshnRNP K interacts with RNA binding motif protein 42 and functions in the maintenance of cellular ATP level during stress conditionsGENES TO CELLS, Issue 2 2009Toshiyuki Fukuda Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a conserved RNA-binding protein that is involved in multiple processes of gene expression, including chromatin remodeling, transcription, RNA splicing, mRNA stability and translation, together with diverse groups of molecular partners. Here we identified a previously uncharacterized protein RNA binding motif protein 42 (RBM42) as hnRNP K-binding protein. RBM42 directly bound to hnRNP K in vivo and in vitro. RBM42 also directly bound to the 3, untranslated region of p21 mRNA, one of the target mRNAs for hnRNP K. RBM42 predominantly localized within the nucleus and co-localized with hnRNP K there. When cells were treated with agents, puromycin, sorbitol or arsenite, which induced the formation of stress granules (SGs), cytoplasmic aggregates of stalled translational pre-initiation complexes, both hnRNP K and RBM42 localized at SGs. Depletion of hnRNP K by RNA interference decreased cellular ATP level following release from stress conditions. Simultaneous depletion of RBM42 with hnRNP K enhanced the effect of the hnRNP K depletion. Our results indicate that hnRNP K and RBM42 are components of SGs and suggest that hnRNP K and RBM42 have a role in the maintenance of cellular ATP level in the stress conditions possibly through protecting their target mRNAs. [source] AMP-activated protein kinase: role in metabolism and therapeutic implicationsDIABETES OBESITY & METABOLISM, Issue 6 2006Greg Schimmack AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge which becomes activated in situations of energy consumption. AMPK functions to restore cellular ATP levels by modifying diverse metabolic and cellular pathways. In the skeletal muscle, AMPK is activated during exercise and is involved in contraction-stimulated glucose transport and fatty acid oxidation. In the heart, AMPK activity increases during ischaemia and functions to sustain ATP, cardiac function and myocardial viability. In the liver, AMPK inhibits the production of glucose, cholesterol and triglycerides and stimulates fatty acid oxidation. Recent studies have shown that AMPK is involved in the mechanism of action of metformin and thiazolidinediones, and the adipocytokines leptin and adiponectin. These data, along with evidence that pharmacological activation of AMPK in vivo improves blood glucose homeostasis, cholesterol concentrations and blood pressure in insulin-resistant rodents, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes, ischaemic heart disease and other metabolic diseases. [source] Augmentation of cellular adenosine triphosphate levels in PC12 cells by extracellular adenosineDRUG DEVELOPMENT RESEARCH, Issue 1 2003Hiroyuki Fujimori Abstract The effects of extracellular adenosine (Ado) on cellular levels of adenosine triphosphate (ATP) in PC12 cells were studied. Ado and inosine but not adenine nucleotides, guanosine, cytosine, uridine, thymidine, and various P1 receptor agonists of Ado, significantly enhanced cellular ATP levels in PC12 cells by about 2.5-fold. The ATP-enhancing effect of Ado was potentiated by dipyridamole, an inhibitor of Ado uptake, and was also observed when PC12 cells were incubated in glucose-free medium. These results suggest that augmentation of cellular ATP levels in PC12 cells by extracellular Ado might be acceleration of ATP synthesis through the Ado salvage system utilizing hypoxanthine-guanine phosphoribosyltransferase rather than Ado kinase, since 5,-iodotubercidin, an Ado kinase inhibitor, had no effect on the enhancement induced by Ado. Drug Dev. Res. 59:8,13, 2003. © 2003 Wiley-Liss, Inc. [source] Calcium-independent cytoskeleton disassembly induced by BAPTAFEBS JOURNAL, Issue 15 2004Yasmina Saoudi In living organisms, Ca2+ signalling is central to cell physiology. The Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane- N,N,N,,N,-tetraacetic acid (BAPTA) has been widely used as a probe to test the role of calcium in a large variety of cell functions. Here we show that in most cell types BAPTA has a potent actin and microtubule depolymerizing activity and that this activity is completely independent of Ca2+ chelation. Thus, the depolymerizing effect of BAPTA is shared by a derivative (D-BAPTA) showing a dramatically reduced calcium chelating activity. Because the extraordinary depolymerizing activity of BAPTA could be due to a general depletion of cell fuel molecules such as ATP, we tested the effects of BAPTA on cellular ATP levels and on mitochondrial function. We find that BAPTA depletes ATP pools and affects mitochondrial respiration in vitro as well as mitochondrial shape and distribution in cells. However, these effects are unrelated to the Ca2+ chelating properties of BAPTA and do not account for the depolymerizing effect of BAPTA on the cell cytoskeleton. We propose that D-BAPTA should be systematically introduced in calcium signalling experiments, as controls for the known and unknown calcium independent effects of BAPTA. Additionally, the concomitant depolymerizing effect of BAPTA on both tubulin and actin assemblies is intriguing and may lead to the identification of a new control mechanism for cytoskeleton assembly. [source] The role of PAS kinase in regulating energy metabolismIUBMB LIFE, Issue 4 2008Huai-Xiang Hao Abstract Metabolic disorders, such as diabetes and obesity, are fundamentally caused by cellular energy imbalance and dysregulation. Therefore, understanding the regulation of cellular fuel and energy metabolism is of great importance to develop effective therapies for metabolic disease. The cellular nutrient and energy sensors, AMPK and TOR, play a key role in maintaining cellular energy homeostasis. Like AMPK and TOR, PAS kinase (PASK) is also a nutrient responsive protein kinase. In yeast, PAS kinase phosphorylates the enzyme Ugp1 and thereby shifts glucose partitioning toward cell wall glucan synthesis at the expense of glycogen synthesis. Consistent with this function, yeast PAS kinase is activated by both cell integrity stress and growth in non-fermentative carbon sources. PASK is also important for proper regulation of glucose metabolism in mammals at both the hormonal and cellular level. In cultured pancreatic ,-cells, PASK is activated by elevated glucose concentrations and is required for glucose-stimulated transcription of the insulin gene. PASK knockdown in cultured myoblasts causes increased glucose oxidation and elevated cellular ATP levels. Mice lacking PASK exhibit increased metabolic rate and resistance to diet-induced obesity. Interestingly, PGC-1 expression and AMPK and TOR activity were not affected in PASK deficient mice, suggesting PASK may exert its metabolic effects through a new mechanism. We propose that PASK plays a significant role in nutrient sensing, metabolic regulation, and energy homeostasis, and is a potential therapeutic target for metabolic disease. © 2008 IUBMB IUBMB Life, 60(4): 204,209, 2008 [source] Regulation of protein phosphatase 1, activity in hypoxia through increased interaction with NIPP1: Implications for cellular metabolismJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2006Kathrina M. Comerford Eukaryotic cells sense decreased oxygen levels and respond by altering their metabolic strategy to sustain non-respiratory ATP production through glycolysis, and thus promote cell survival in a hypoxic environment. Protein phosphatase 1 (PP1) has been recently implicated in the governance of the rational use of energy when metabolic substrates are abundant and contributes to cellular recovery following metabolic stress. Under conditions of hypoxia, the expression of the gamma isoform of PP1 (PP1,), is diminished, an event we have hypothesized to be involved in the adaptive cellular response to hypoxia. Decreased PP1, activity in hypoxia has a profound impact on the activity of the cAMP response element binding protein (CREB), a major transcriptional regulator of metabolic genes and processes. Here, we demonstrate a further mechanism leading to inhibition of PP1 activity in hypoxia which occurs at least in part through increased association with the nuclear inhibitor of PP1 (NIPP1), an event dependent upon decreased basal cAMP/PKA-dependent signaling. Using a dominant negative NIPP1 construct, we provide evidence that NIPP1 plays a major role in the regulation of both CREB protein expression and CREB-dependent transcription in hypoxia. Furthermore, we demonstrate functional sequellae of such events including altered gene expression and recovery of cellular ATP levels. In summary, we demonstrate that interaction with NIPP1 mediates decreased PP1, activity in hypoxia, an event which may constitute an inherent part of the cellular oxygen-sensing machinery and may play a role in physiologic adaptation to hypoxia. J. Cell. Physiol. 209: 211,218, 2006. © 2006 Wiley-Liss, Inc. [source] | |||||||||||||