Disease relevance of Ak1

• Studies of photosensitization of AK in different mitochondrial preparations demonstrated that inhibition of activity was evident only when mitochondrial membranes containing sequestered porphyrins were present in the reaction mixture [1].
• The effects of altered estrogenic environments on creatine kinase (CK) and adenylate kinase (AK) were studied in two rodent mammary tumor systems, R3230AC and primary 7,12-dimethylbenz(a)anthracene (DMBA)-induced carcinomas, to determine whether response of these enzymes could be related to their hormone dependence [2].
• Further, in hypertrophy, the reduced creatine kinase and adenylate kinase activities limited energy delivery to the nuclear pore [3].
• Increase of adenylate kinase isozyme 1 protein during neuronal differentiation in mouse embryonal carcinoma P19 cells and in rat brain primary cultured cells [4].
• Rigor, but not myosin ATPase, was inhibited by acidosis (pH 6.2), indicating reduced efficiency of cross-bridge cycling, while both parameters were stimulated by ADP (< or = 1 mM) and unaffected by inorganic phosphate (Pi, 30 mM), AMP, Mg2+, lactate or inhibition of adenylate kinase with diadenosine pentaphosphate [5].

High impact information on Ak1

• The adenylate kinase and pyruvate kinase activities in the liver remained unchanged [6].
• This result implies that p34cdc2 and A-kinase inhibition have complementary and additive effects on the process of nuclear envelope breakdown in living fibroblasts, a conclusion further supported by our observation of a pronounced dephosphorylation of lamins A and C in cells after injection of PKi(m) [7].
• Taken together, these data suggest that down-regulation of A-kinase is a distinct and essential event in the induction of mammalian cell mitosis which co-operates with the p34cdc2 pathway [7].
• Inhibiting cAMP-dependent protein kinase (A-kinase) in mammalian fibroblasts through microinjection of a modified specific inhibitor peptide, PKi(m) or the purified inhibitor protein, PKI, resulted in rapid and pronounced chromatin condensation at all phases of the cell cycle [7].
• With deficient adenylate kinase, nucleoside diphosphate kinase, which secures phosphoryl exchange between ATP and GTP, was unable to sustain nuclear import [8].

Chemical compound and disease context of Ak1

• The response to Photofrin II-induced photosensitization on the activities of mitochondrial monoamine oxidase (MAO) and adenylate kinase (AK) were studied in order to gain further insight into site specific effects [1].
• When mouse embryonal carcinoma P19 cells were differentiated by retinoic acid into neural cells, the amount of AK1 protein and enzyme activity increased about fivefold concomitantly with neurofilament (NF) [4].
• Mechanisms of toxicity of 3'-azido-3'-deoxythymidine. Its interaction with adenylate kinase [9].
• While prostaglandins A2 and E2 stimulated, prostaglandins A1 and F2alpha inhibited, and prostaglandin E1 was without effect on the hepatoma adenylate kinase [10].
• The present study was done to determine: (1) regional (cortex, red medulla and papilla) changes in ATP, ADP and AMP resulting from periods of ischemia of 30-300 s; (2) whether ischemic changes in adenine nucleotides or lactate were modified by hypertonic saline loading, and (3) whether adenylate kinase activity was present in each region [11].

Biological context of Ak1

• Adenylate kinase (AK) is known to play an important role in homeostasis of adenine nucleotide metabolism [12].
• In the olfactory bulb, AK1 gene expression was enhanced in the early postnatal days, whereas it remained low in the cerebellum during the first 10 postnatal days [13].
• The acute effects of insulin, adenosine, and isoproterenol on the activity, subcellular distribution, and phosphorylation state of the GLUT4 glucose transporter isoform were investigated in rat adipocytes under conditions carefully controlled to monitor changes in cAMP-dependent protein kinase (A-kinase) activity [14].
• When only Pi and ADP are added and formation of ATP from added ADP by adenylate kinase and subsequent ATP hydrolysis are adequately blocked, no Pi in equilibrium HOH exchange can be observed, demonstrating a requirement of energization by ATP binding and cleavage for such an exchange [15].
• The first characterization of the kinetics and subcellular compartmentation of adenylate kinase activity in intact muscle has been accomplished using rat diaphragm equilibrated with [18O]water [16].

Anatomical context of Ak1

• We further examined developmental changes in mRNAs and enzyme activities of AK isozymes in rat skeletal muscle and liver [12].
• Utilizing intact mitochondria in vitro, both MAO, located on the cytoplasmic side of the outer mitochondrial membrane, and AK, located in the intermembrane space, were inhibited by exposure to Photofrin II plus light; inhibition was drug-dose and light-dose dependent [1].
• Prostates from neonatal rats and castrated adult male rats exhibited patterns of creatine kinase and adenylate kinase similar to those of the undifferentiated tumor [17].
• Receptor-mediated endocytosis of lactate dehydrogenase M4 by liver macrophages: a mechanism for elimination of enzymes from plasma. Evidence for competition by creatine kinase MM, adenylate kinase, malate, and alcohol dehydrogenase [18].
• These results provide new and exciting evidence that cAMP acts in granulosa cells by A kinase-dependent and -independent mechanisms, each of which controls specific kinase cascades [19].

Associations of Ak1 with chemical compounds

• In this paper, data are presented which demonstrate that adenylate kinase and creatine kinase are oncodevelopmental enzymes in the rat prostate [17].
• Higher doses of Photofrin II had no further effect on AK activity [1].
• In a low ionic environment, when the outer membrane integrity was damaged either by gradually decreasing the tonicity of the medium or by stepwise addition of Triton X-100, either chymotrypsin or trypsin caused virtually parallel inhibition of glycerophosphate acyltransferase and adenylate kinase [20].
• DNP and NaF did not affect the equilibrium constant for the myokinase catalyzed reaction and the intracellular concentration of hypoxanthine was stable, confirming the integrity of the cells during the experiments [21].
• At a concentration of 125 nM, Bax caused the release of the intermembranous proteins cytochrome c and adenylate kinase and the release from the matrix of sequestered calcein, effects prevented by the inhibitor of the PTP cyclosporin A (CSA) [22].

Physical interactions of Ak1

• The studies reveal that a significant fraction of the ADP generated by either adenylate kinase in the intermembrane space or by outer membrane bound hexokinase isozyme I, is not accessible to extramitochondrial pyruvate kinase [23].

Regulatory relationships of Ak1

• Overexpression of NeuroD in PC12 cells alters morphology and enhances expression of the adenylate kinase isozyme 1 gene [24].

Other interactions of Ak1

• AK1 mRNA accumulated at the prenatal stage and further increased during development, while AK3 mRNA was at high levels during the fetal stage and remained fairly constant during development [12].
• 4) Exposure of primary rat islets or 832/13 cells to the inflammatory cytokines causes cell death as evidenced by the release of adenylate kinase activity into the cell medium, with no attendant increase in caspase 3 activation or annexin V staining [25].
• Rat ovarian granulosa cell as a site of endothelin reception and action: attenuation of gonadotropin-stimulated steroidogenesis via perturbation of the A-kinase signaling pathway [26].
• These data demonstrate that, like IGF-I, IL-6 may be able to act as a growth factor through activation of a mitogenic signal transduction pathway different from A-kinase in FRTL-5 cells [27].
• In contrast, CA074Me did not affect levels of myogenin, an early marker of myogenesis, or levels of cathepsin L type and myokinase activities, two nonspecific enzymes [28].

Analytical, diagnostic and therapeutic context of Ak1

• We isolated cDNAs for rat AK isozymes (AK1, AK2, and AK3), determined their mRNAs in rat tissues by Northern blot analysis, and measured the isozyme activities [12].
• Compared to cytochrome c oxidase, located in the inner mitochondrial membrane and which displayed a sustained inhibition of activity, we suggest that inhibition of MAO or AK activities probably does not contribute to the tumor cytotoxicity under the usual conditions used for photodynamic therapy [1].
• Interfering cytosolic adenylate kinase was extracted from the cytosol by affinity chromatography on Ap5A-agarose, and remaining traces of enzyme activity were inhibited with (+)-catechin [29].
• RT-PCR analysis indicated the enhanced level of AK1 mRNA in NeuroD-producing PC12 cells [24].
• Electrophoretic mobility shift assays demonstrated that NeuroD was able to interact with a proximal E-box element of the AK1 promoter [24].

References