As a DNA receptor in the cytoplasm,cyclic GMP-AMP synthase (cGAS) can recognize abnormal DNA in the cytoplasm and activate stimulator of interferon genes (STING) to regulate the immune response. The recent studies have demonstrated that this pathway plays a role in non-infectious inflammatory diseases by promoting the expression of type Ⅰ interferon and interferon-stimulated gene.This article reviews the activation and regulation of cGAS-STING pathway in multiple systems and the effect of this pathway on the occurrence and progression of non-infectious inflammatory diseases,providing theoretical reference for future application of cGAS-STING pathway-related drugs in non-infectious inflammatory diseases.
Humans ; Interferons ; Membrane Proteins/metabolism* ; Noncommunicable Diseases ; Nucleotides, Cyclic ; Nucleotidyltransferases/metabolism* ; Signal Transduction

The purpose of this study is to investigate the effect of methylprednisolone(M.P.) on the alterations of ATP, sum of adenosine nucleotides, adenylate energy charge(E.C.), glucose and lactate in the cats with acute focal ischemic cerebral edema. The acute occlusion of left middle cerebral artery(MCA) of forty cats for 1,3 and 5 hours respectively were accomplished by applying Heifetz clip through the transorbital approach operating microscope. Twelve cats were not recirculated as a untreated group, twelve cats were recirculated for 2 hours as a ecirculation group and twelve cats were recirculated for 2 hours and given M.P.(15mg/kg) at 30 minutes after occlusion initially, and then every one and a half hour as a treatment group. The experimental results are as follows. 1) In 1-hour untreated group, ATP was reduced to 34.0%, sum of adenosine nucleotides reduced to 72.2%, adenylate E.C. reduced to 60.6%, glucose reduced to 67.3% and lactate increased to 156.6% of the control value. In the recirculation group, ATP was reduced to 42.0%, sum of adenosine nucleotides reduced to 82.4%, adenylate E.C. reduced to 74.3%, glucose increased to 552.7% and lactate decreased to 79.8%. In the treatment group, ATP was increased to 143.9%, sum of adenosine nucleotides increased to 153.9%, adenylate E.C. decreased to 92.9%, glucose increased to 3334.5% and lactate decreased to 74.6%. 2) In 3-hour untreated group, ATP was decreased to 24.9%, sum of adenosine nucleotides reduced to 22.9%, adenylate E.C. reduced to 58.6%, glucose decreased to 45.5% and lactate increased to 161.3% of the control value. In the recirculation group, ATP reduced to 32.9%, sum of adenosine nucleotides reduced to 28.6%, adenylate E.C. reduced to 71.4%, glucose rose to 520.0% and lactate to 135.3% of the control value. In the treatment group, ATP reduced to 99.5%, sum of adenosine nucleotides increased to 103.5%, adenylate E.C. decreased to 84.3%, glucose rose to 1187.3% and lactate increased to 101.2%. 3) In 5-hour untreated group, ATP decreased to 5.3%, sum of adenosine nucleotides reduced to 9.0%, adenylate E.C. reduced to 58.6%, glucose decreased to 25.5% and lactate increased to 187.9%. In the recirculation group, ATP decreased to 4.4%, sum of adenosine nucleotides decreased to 5.8%, adenylate E.C. decreased to 57.1%. In the treatment group, ATP was reduced to 11.2%, sum of adenosine nucleotides and adenylate E.C. reduced to 70.0%, glucose rose to 103.6% and lactate to 157.2% of the control value. As the results shown above, the therapeutic beneficial effects of M.P. were observed in cats of 1 or 3-hour occlusion of MCA with 2-hour recirculation.
Adenosine ; Adenosine Triphosphate ; Animals ; Brain Edema ; Cats ; Energy Metabolism* ; Glucose ; Ischemia* ; Lactic Acid ; Methylprednisolone* ; Nucleotides

It is the purpose of this experimental study to investigate the alterations of the amount of adenosine nucleotides and adenylate energy charge in the acute focal cerebral ischemia of cats utilizing high performance liquid chromatography and to make a comparative study of protective effects of recirculation and combined therapy with mannitol, steroid and barbiturate. Acute focal cerebral ischemia in cats was induced by occlusion of the left middle cerebral artery through the postorbital technique. The experimental animals were divided into four groups according to the duration of occlusion time. The experimental results are obtained as follows: 1) In 1, 3 and 5 hour-occlusion groups, amount of adenosine triphosphate and summation of adenosine nucleotides decreased significantly to 21.4%, 5% & 0%, 44.0%, 29.9% & 10.8% of the sham control, respectively. Also in these groups adenylate energy charge decreased significantly to 62.7%, 38.7% and 30.7% of the sham control, respectively. It was suggested that the longer duration of occlusion time was, the more amount of adenosine triphosphate, summation of adenosine nucleotides and adenylate energy charge decreased significantly. 2) In 1 and 3 hour-occlusion groups, 2 hour-recirculation increased significantly amount of adenosine triphosphate and summation of adenosine nucleotides to 37.4% & 29.4%, and 62.1% & 58.3% of the sham control, respectively. Also in these groups recirculation increased significantly adenylate energy charge to 70.7% and 65.3% of the sham control, respectively. Whereas there was a slight increase of adenylate energy charge after recirculation in 5 hour-occlusion group, but not significant. 3) In the groups of recirculation following 5 hour-occlusion, pretreatment of combination of mannitol and steroid, or mannitol, steroid and barbiturate increased significantly amount of adenosine triphosphate, summation of adenosine nucleotides, and adenylate energy charge to 57.2% or 66.1%, 80.9% or 83.5% and 82.7% or 84.0% of sham control, respectively.
Adenosine ; Adenosine Triphosphate ; Animals ; Brain Ischemia ; Cats ; Chromatography, Liquid ; Mannitol ; Metabolism* ; Middle Cerebral Artery ; Nucleotides

In the 1920's, Warburg reported an observation that cancer cells depend on glycolysis even in the presence of available oxygen likely due to impaired function of mitochondria. Since then, this Warburg s effect has been the most important hypothesis in cancer metabolism and is considered as a seventh hallmark of many human cancers. Aerobic glycolysis was originally attributable to increased bioenergetic needs in rapidly proliferating cancer cells. Recently, biosynthetic aspects of aerobic glycolysis, which reprograms cancer metabolism to synthesize macromolecules such as nucleotides, fatty acids, amino acids, etc., are under active investigation. Introduction of positron emission tomography (PET) and metabolic radiotracers including F-18 flurorodeoxyglucose (FDG) and C-11 acetate made it possible to image cancer metabolism in vivo and to renew the interests on this issue. Studies have found that cancer cells with highly glycolysis features are associated with resistance to many chemotherapeutic regimens and radiation treatment. Therefore, development of glycolytic inhibitors can have an incremental effect to conventional treatments. In addition, functional imaging with metabolic radiotracers will continuously play important roles in detecting cancers and monitoring therapeutic responses to novel anti-metabolic approaches to cancer cells.
Amino Acids ; Electrons ; Energy Metabolism ; Fatty Acids ; Glycolysis ; Humans ; Mitochondria ; Nucleotides ; Oxygen ; Positron-Emission Tomography

Glucose and lipid metabolism is the most fundamental metabolic activity of higher organisms. This process is affected by both genetic polymorphisms and environmental factors. Excessive uptake and accumulation of lipids lead to obesity and disorder of glucose metabolic homeostasis characterized by insulin resistance and hyperglycemia, suggesting that the cross-regulation between lipid and glucose metabolism happens precisely at organ, cellular and molecular levels by known mechanisms. Adenine nucleotides and their metabolites have emerged as mediators in the mutual regulation of glucose and lipid metabolism. This review summarizes the roles of purinergic signaling induced by fatty acids in glucose metabolism and the development of type 2 diabetes.
Adenine Nucleotides ; Diabetes Mellitus, Type 2 ; Glucose ; Homeostasis ; Humans ; Insulin Resistance ; Lipid Metabolism

OBJECTIVETo detect the structure and chemical characteristics of the adduct from the reaction of p-benzoquinone (BQ) with deoxyguanoside (dGMP).

METHODSdGMP and calf thymus DNA were reacted with BQ in buffered solutions with neutral pH, the reaction products were separated and purified by high performance liquid chromatograph (HPLC), and then characterized by UV spectroscopy and mass spectrometry.

RESULTSThe reaction of BQ with dGMP yielded two adduct products (Ad(1) and Ad(2) respectively). The characterized results of Ad(1) suggested that BQ reacted at the N-1 and N(2) position of dGMP by losing one H(2)O molecule, the molecular weight of Ad(1) was 437, and the molecular formula was C(16)H(16)O(8)N(5)P. Ad(1) could also be detected from calf thymus DNA reacted with BQ in vitro, which possessed the same elution profile by HPLC analysis. Meanwhile, Ad(2) was detected in the experimental condition. It was proposed that Ad(2) was formed by BQ reacted at the N-9 position of dGMP by losing one molecule of deoxyribose, the molecular weight was 241, and the molecular formula was C(11)H(7)O(2)N(5).

CONCLUSIONThe structure of one major adduct from reaction of BQ with DNA is (3'-OH)-1, N(2)-C(6)H(5)CH-2'-deoxyguanosine-5'-monophosphate.

Benzoquinones ; metabolism ; DNA Adducts ; chemistry ; Deoxyguanine Nucleotides ; metabolism ; Hydrogen-Ion Concentration ; Mass Spectrometry ; Molecular Weight ; Spectrophotometry, Ultraviolet

OBJECTIVETo study the changes of neutral alpha-glucoside activity in the epididymis of heroin-dependent and heroin-withdrawal rats, and to investigate the effects of intervention with purine nucleotide (AMP and GMP).

METHODSEighty Wistar rats were randomly divided into 8 groups of equal number, control, nucleotide, heroin, heroin + nucleotide, 3 d withdrawal, 9 d withdrawal, 3 d nucleotide (nucleotide administrated for 3 days after heroin withdrawal) and 9 d nucleotide (nucleotide administrated for 9 days after heroin withdrawal). Neutral alpha-glucosidase activity in the epididymis was detected in each group of rats.

RESULTSCompared with the control group, neutral alpha-glucoside activity was markedly decreased in the heroin group (P < 0.05), and also in the 3 d and 9 d withdrawal groups, although with no significant differences (P > 0.05).

CONCLUSIONHeroin reduces neutral alpha-glucoside activity in the epididymis of rats, and this effect may continue for some time after drug withdrawal, while purine nucleotide can keep neutral alpha-glucosidase activity in a relatively stable state.

Animals ; Epididymis ; chemistry ; Heroin ; adverse effects ; Heroin Dependence ; metabolism ; Male ; Purine Nucleotides ; pharmacology ; Rats ; Rats, Wistar ; alpha-Glucosidases ; metabolism

Magnetotactic bacteria (MTB), a group of phylogenetically diverse organisms that use their unique intracellular magnetosome organelles to swim along the Earth's magnetic field, play important roles in the biogeochemical cycles of iron and sulfur. Previous studies have revealed that the bacterial actin protein MamK plays essential roles in the linear arrangement of magnetosomes in MTB cells belonging to the Proteobacteria phylum. However, the molecular mechanisms of multiple-magnetosome-chain arrangements in MTB remain largely unknown. Here, we report that the MamK filaments from the uncultivated 'Candidatus Magnetobacterium casensis' (Mcas) within the phylum Nitrospirae polymerized in the presence of ATP alone and were stable without obvious ATP hydrolysis-mediated disassembly. MamK in Mcas can convert NTP to NDP and NDP to NMP, showing the highest preference to ATP. Unlike its Magnetospirillum counterparts, which form a single magnetosome chain, or other bacterial actins such as MreB and ParM, the polymerized MamK from Mcas is independent of metal ions and nucleotides except for ATP, and is assembled into well-ordered filamentous bundles consisted of multiple filaments. Our results suggest a dynamically stable assembly of MamK from the uncultivated Nitrospirae MTB that synthesizes multiple magnetosome chains per cell. These findings further improve the current knowledge of biomineralization and organelle biogenesis in prokaryotic systems.
Actins ; chemistry ; metabolism ; Adenosine Triphosphate ; metabolism ; Bacteria ; classification ; metabolism ; Bacterial Proteins ; chemistry ; metabolism ; Magnetospirillum ; classification ; metabolism ; Nucleotides ; metabolism ; Phylogeny ; Substrate Specificity

C-Terminal carboxyl methylation of a human placental 23 kDa protein catalyzed by membrane-associated methyltransferase has been investigated. The 23 kDa protein substrate methylated was partially purified by DEAE-Sephacel, hydroxyapatite and Sephadex G-100 gel filtration chromatographies. The substrate protein was eluted on Sephadex G-100 gel filtration chromatography as a protein of about 29 kDa. In the absence of Mg2+, the methylation was stimulated by guanine nucleotides (GTP, GDP and GTPgammaS), but in the presence of Mg2+, only GTPgammaS stimulated the methylation which was similar to the effect on the G25K/rhoGDI complex. AFC, an inhibitor of C-terminal carboxyl methylation, inhibited the methylation of human placental 23 kDa protein. These results suggests that the substrate is a small G protein different from the G25K and is methylated on C-terminal isoprenylated cysteine residue. This was also confirmed by vapor phase analysis. The methylated substrate protein was redistributed to membrane after in vitro methylation, suggesting that the methylation of this protein is important for the redistribution of the 23 kDa small G protein for its putative role in intracellular signaling.
Cysteine/metabolism* ; Female ; GTP-Binding Proteins/metabolism* ; Guanine Nucleotides/pharmacology ; Human ; Methylation ; Placenta/metabolism* ; Placenta/enzymology ; Pregnancy ; Pregnancy Proteins/metabolism* ; Protein Methyltransferases/metabolism*

Idiopathic asthenozoospermia, a common factor in male infertility, is characterized by altered sperm motility function in fresh ejaculate. Although the β-defensin 126 (DEFB126) protein is associated with asthenozoospermia, DEFB126 gene polymorphisms have not been extensively studied. Therefore, the association between DEFB126 gene polymorphisms and asthenozoospermia requires further investigation. Screening was performed by semen analysis, karyotype analysis, and Y microdeletion detection, and 102 fertile men and 106 men with asthenozoospermia in Chengdu, China, were selected for DEFB126 gene sequence analyses. Seven nucleotide mutations and two nucleotide deletions in the DEFB126 gene were detected. rs11467417 (317-318 del/del), rs11467497 (163-166 wt/del), c.152T>C, and c.227A>G were significantly different between the control and asthenozoospermia groups, likely representing high-risk genetic factors for asthenozoospermia among males. DEFB126 expression was not observed in sperm with rs11467497 homozygous deletion and was unstable in sperm with rs11467417 homozygous deletion. The rs11467497 four-nucleotide deletion leads to truncation of DEFB126 at the carboxy-terminus, and the rs11467417 binucleotide deletion produces a non-stop messenger RNA (mRNA). The above deletions may be responsible for male hypofertility and infertility by reducing DEFB126 affinity to sperm surfaces. Based on in silico analysis, the amino acids 51M and 76K are located in the highly conserved domain; c.152T>C (M51T) and c.227A>G (K76R) are predicted to be damaging and capable of changing alternative splice, structural and posttranslational modification sites of the RNA, as well as the secondary structure, structural stability, and hydrophobicity of the protein, suggesting that these mutations are associated with asthenozoospermia.
Male ; Humans ; Asthenozoospermia/metabolism* ; Sperm Motility/genetics* ; Homozygote ; Polymorphism, Single Nucleotide ; Semen ; Sequence Deletion/genetics* ; Spermatozoa/metabolism* ; Nucleotides/metabolism* ; beta-Defensins/metabolism*