ubiquinone and phenylacetic-acid

Strain Kp5.2(T) is an aerobic, Gram-negative soil bacterium that was isolated in Freiberg, Saxony, Germany. The cells were motile and rod-shaped. Optimal growth was observed at 20-30 °C. The fatty acids of strain Kp5.2(T) comprised mainly C18 : 1ω7c and summed feature 3 (C16 : 1ω7c/iso-C15 : 0 2-OH). The major respiratory quinone was Q-10. The major polar lipids of strain Kp5.2(T) were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and sphingoglycolipid. The G+C content of the genomic DNA was 63.7%. Sequencing of the 16S rRNA gene of strain Kp5.2(T) allowed its classification into the family Sphingomonadaceae, and the sequence showed the highest similarity to those of members of the genus Sphingopyxis, with Sphingopyxis italica SC13E-S71(T) (99.15% similarity), Sphingopyxis panaciterrae Gsoil 124(T) (98.96%), Sphingopyxis chilensis S37(T) (98.90%) and Sphingopyxis bauzanensis BZ30(T) (98.51%) as the nearest neighbours. DNA-DNA hybridization and further characterization revealed that strain Kp5.2(T) can be considered to represent a novel species of the genus Sphingopyxis. Hence, the name Sphingopyxis fribergensis sp. nov. is proposed, with the type strain Kp5.2(T) ( = DSM 28731(T) = LMG 28478(T)).

Topics: Bacterial Typing Techniques; Base Composition; DNA, Bacterial; Fatty Acids; Germany; Molecular Sequence Data; Nucleic Acid Hybridization; Phenylacetates; Phospholipids; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Soil Microbiology; Sphingomonadaceae; Styrene; Ubiquinone

Malignant gliomas, the most common form of primary brain tumors, are highly dependent on the mevalonate (MVA) pathway for the synthesis of lipid moieties critical to cell replication. Human glioblastoma cells were found to be uniquely vulnerable to growth arrest by lovastatin, a competitive inhibitor of the enzyme regulating MVA synthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase. The sodium salt of phenylacetic acid (NaPA), an inhibitor of MVA-pyrophosphate decarboxylase, the enzyme that controls MVA use, acted synergistically with lovastatin to suppress malignant growth. When used at pharmacologically attainable concentrations, the two compounds induced profound cytostasis and loss of malignant properties such as invasiveness and expression of the transforming growth factor-beta 2 gene, coding for a potent immunosuppressive cytokine. Supplementation with exogenous ubiquinone, an end product of the MVA pathway, failed to rescue the cells, suggesting that decreased synthesis of intermediary products are responsible for the antitumor effects observed. In addition to blocking the MVA pathway, lovastatin alone and in combination with NaPA increased the expression of the peroxisome proliferator-activated receptor, a transcription factor implicated in the control of lipid metabolism, cell growth, and differentiation. Our results indicate that targeting lipid metabolism with lovastatin, used alone or in combination with the aromatic fatty acid NaPA, may offer a novel approach to the treatment of malignant gliomas.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cell Division; Drug Synergism; Glioma; Humans; Lipid Metabolism; Lovastatin; Mevalonic Acid; Neoplasm Invasiveness; Phenylacetates; Tumor Cells, Cultured; Ubiquinone