Curcumin modulates the apolipoprotein B mRNA editing by coordinating the expression of cytidine deamination to uridine editosome components in primary mouse hepatocytes

Curcumin, an active ingredient of Curcuma longa L., can reduce the concentration of low-density lipoproteins in plasma, in different ways. We had first reported that curcumin exhibits hypocholesterolemic properties by improving the apolipoprotein B (apoB) mRNA editing in primary rat hepatocytes. However, the role of curcumin in the regulation of apoB mRNA editing is not clear. Thus, we investigated the effect of curcumin on the expression of multiple editing components of apoB mRNA cytidine deamination to uridine (C-to-U) editosome. Our results demonstrated that treatment with 50 µM curcumin markedly increased the amount of edited apoB mRNA in primary mouse hepatocytes from 5.13%–8.05% to 27.63%–35.61%, and significantly elevated the levels of the core components apoB editing catalytic polypeptide-1 (APOBEC-1), apobec-1 complementation factor (ACF), and RNA-binding-motif-protein-47 (RBM47), as well as suppressed the level of the inhibitory component glycine-arginine-tyrosine-rich RNA binding protein. Moreover, the increased apoB RNA editing by 50 µM curcumin was significantly reduced by siRNA-mediated APOBEC-1, ACF, and RBM47 knockdown. These findings suggest that curcumin modulates apoB mRNA editing by coordinating the multiple editing components of the editosome in primary hepatocytes. Our data provided evidence for curcumin to be used therapeutically to prevent atherosclerosis.

Biological roles of adenosine deaminase acting on RNA and their relationship with human diseases / 中南大学学报(医学版)

RNA editing, especially A-to-I RNA editing, is a common post-transcriptional modification in mammals. Adenosine deaminase acting on RNA (ADAR) is a key protein for A-to-I editing, which converts the adenosine group of a double-stranded RNA to creatinine group by deaminating it, resulting in a change of nucleotide sequence. There are 3 types of ADARs (ADAR1, ADAR2, ADAR3) that have been found in recent years. The abnormalities of ADARs are closely related to many human diseases such as viral infections, metabolic diseases, nervous system diseases, and tumors.

Recent advances in the study of mechanism of APOBEC3G against virus / 药学学报

APOBEC3 is a class of cytidine deaminase, which is considered as a new member of the innate immune system, and APOBEC3G belongs to this family. The research about APOBEC3G is a new direction of innate immune defense mechanism against virus. APOBEC3G has the restrictive activity on many viral replications, which deaminates dC to dU in the viral genome and then induces extensive hypermutation. APOBEC3G can also interrupt viral replication at several phases such as reverse transcription, replication, nucleocapsid and so on by non-deamination mechanisms. However, virus can encode viral proteins to counteract the restriction activity of APOBEC3G. Elucidation of the antagonistic interaction between APOBEC3G and the virus will be contributed to development of new antiviral drugs in the future.

Fungal and Plant Phenylalanine Ammonia-lyase

L-Phenylalanine is one of the essential amino acids that cannot be synthesized in mammals in adequate amounts to meet the requirements for protein synthesis. Fungi and plants are able to synthesize phenylalanine via the shikimic acid pathway. L-Phenylalanine, derived from the shikimic acid pathway, is used directly for protein synthesis in plants or metabolized through the phenylpropanoid pathway. This phenylpropanoid metabolism leads to the biosynthesis of a wide array of phenylpropanoid secondary products. The first step in this metabolic sequence involves the action of phenylalanine ammonia-lyase (PAL). The discovery of PAL enzyme in fungi and the detection of 14CO2 production from 14C-ring-labeled phenylalanine and cinnamic acid demonstrated that certain fungi can degrade phenylalanine by a pathway involving an initial deamination to cinnamic acid, as happens in plants. In this review, we provide background information on PAL and a recent update on the presence of PAL genes in fungi.

Clinical Utility of Adenosine Deaminase Isoenzyme Determinations in Leukemia / 대한임상병리학회지

BACKGROUND: Adenosine deaminase (ADA), an enzyme involved in purine metabolism, catalyzes the hydrolytic deamination of adenosine or 2-deoxyadenosine to inosine or 2-deoxyinosine. Human ADA consists of three molecular forms: ADA1, ADA1+CP, and ADA2. The two ADA isoenzymes represent two different gene products and have different tissue distributions, and their concentrations in serum appear to reflect different pathological conditions or physiological responses. Elevation of serum ADA activity has been described especially in leukemia and lymphoma. The purpose of this study was to evaluate the clinical utility of ADA isoenzyme determination in the diagnosis of leukemia. METHODS: We studied the activity of serum ADA and its isoenzyme in 44 leukemic patients. The study population consisted of 17 patients with acute lymphoblastic leukemia (ALL), 23 with acute myeloid leukemia (AML), and 4 with chronic myelogenous leukemia (CML). ADA isoenzyme was measured by erythro-9- (2-hydroxy-3-nonyl) adenine [EHNA] inhibitory assay using the Hitachi 7170 autoanalyzer. RESULTS: The rates of abnormally high total ADA activity were 100% for ALL, 60.8% for AML, and 50% for CML. In isoenzyme pattern, there was a clear difference between ALL and AML. High level of ADA1 activity was found in patients with ALL (P <0.01). The ADA1/ADA2 ratio was significantly higher (P <0.001) in ALL than AML. There was a correlation between ADA1 and absolute number of peripheral blasts in AML (r=0.840). CONCLUSIONS: It is concluded that the measurement of ADA isoenzyme may be a useful biochemical marker for leukemic diagnosis.

Valor diagnóstico de la determinación de la actividad de adenosina desaminasa sérica en tuberculosis pulmonar / Average value of serum adenosine deaminase in pulmonary tuberculosis

Con la finalidad de conocer el valor diagnóstico de la determinación de la actividad de adenosina desaminasa sérica en tuberculosis pulmonar, enrolamos 20 pacientes y 20 sujetos sanos pareados por edad y sexo. La edad promedio fue 41.9 mas menos 22.0 años y el tiempo de enfermedad 4.2 mas menos 3.4 meses. El diagnóstico de tuberculosis pulmonar se basó en la clínica, frotis de esputo para bacilos ácido alcohol resistentes (prueba de oro) y radiología de tórax. El valor promedio de adenosina desaminasa sérica de los pacientes con tuberculosis pulmonar fue 33.9 mas menos 21.00 U/L y de los sujetos sanos 20.8 mas menos 7.8 U/L (p menor 0.05). El punto de corte para considerar la prueba como positiva fue mayor menos 36.4 U/L. Con este valor la sensibilidad fue 30 por ciento, especificidad 90 por ciento, valor predictivo positivo 75 por ciento y valor predictivo negativo 56.25 por ciento

A colorimetric method for assay of serotonin deamination by monoamine oxidase.

The present method involves conversion of the aldehyde produced, as a result of serotonin deamination by monoamine oxidase, to its 2:4 dinitrophenyl hydrazone derivative which gives a stable, bright yellow colour in alkaline solution and can be measured colorimetrically. The derivative is however unstable in the acidic medium and has to be extracted into an organic solvent immediately. The details of the method and its standardization are discussed.

Further Studies of Adenosine Deaminase in the Human Skin (II) / 대한피부과학회지

Adenosine deaminase (adenosine aminohydrolase, E.C.3. 5. 4. 4; ADA), which catalyzes the deamination of adenosine to yield inosine and ammonia, was characterized in the human penile foreskin. ADA was found to be present in both layers of the skin with slightly higher activity in the epidermis(Epidermis; (7. 2+2. 3) * 10-4 unit/mg protein, Dermis;(5. 7 +1. 9) *10-4 unit/mg protein). The enzyme exhibited a broad pH optimum from 6. 5 to 8. 0 in both layers of the skin, and was heat-labile, being completely inactivated by heat treatment at 70C-75 C for 10 minutes. In contrast to the ADA of other tissue, the enzyme was inhibited by 2 mM of Cu2+, Fe2+ and Co2+ at pH7. 0 in both layers of the skin. The inhibitory effect of Cu2+ on the enzyme was stronger than other metal ions, and the enzyme was completely inactivated by 20 mM of Cu2+ in both layers. The Cu2+ inhibited enzyme activities which were recovered by adding EDTA. From the above results, it is suggested that the enzyme in both layers of the skin are consisted of same types of isozymes.

Adenosine Deaminase in Human Skin / 대한피부과학회지

Adenosine deaminase (adenosine aminohydrolase, AL)A), which catalyzes the deamination of adenosine to yield inosine and amrnonia, was assayed in human penile foreskin. The skin tissue was separated into two layers; epidermis and dermis. They were sliced with scissors into gel state, 4 volumes of 0.05M phosphate buffer solution were added and the tissue homogenized. After centrifugation at 4,000xg for 5 minutes, the supernatant was used as an enzyme solution. ADA activity was measured according to the method f Giuseppe" ADA was found to be present in both layers (epidermis; 0.24 OD/mg protein, dermis; 0.19 OD/mg protein) with slightly higher activity in the epidermis. As in earlier reports, it was found that ADA in the skin showed nearly even activity in the pH range of 5.0-8.0. Considering the significance of ADA in immunological function, the presence of ADA in the skin suggests that the tissue may participate in the immune function.