Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Muscle-specific isoform of the mitochondrial ATP synthase gamma subunit (F(1)gamma) was generated by alternative splicing, and exon 9 of the gene was found to be lacking particularly in skeletal muscle and heart tissue. Recently, we reported that alternative splicing of exon 9 was induced by low serum or acidic media in mouse myoblasts, and that this splicing required de novo protein synthesis of a negative regulatory factor (Ichida, M., Endo, H., Ikeda, U., Matsuda, C., Ueno, E., Shimada, K., and Kagawa, Y. (1998) J. Biol. Chem. 273, 8492-8501; Hayakawa, M., Endo, H., Hamamoto, T., and Kagawa, Y. (1998) Biochem. Biophys. Res. Commun. 251, 603-608). In the present report, we identified a cis-acting element on the muscle-specific alternatively spliced exon of F(1)gamma gene by an in vivo splicing system using cultured cells and transgenic mice. We constructed a F(1)gamma wild-type minigene, containing the full-length gene from exon 8 to exon 10, and two mutants; one mutant involved a pyrimidine-rich substitution on exon 9, whereas the other was a purine-rich substitution, abbreviated as F(1)gamma Pu-del and F(1)gamma Pu-rich mutants, respectively. Based on an in vivo splicing assay using low serum- or acid-stimulated splicing induction system in mouse myoblasts, Pu-del mutation inhibited exon inclusion, indicating that a Pu-del mutation would disrupt an exonic splicing enhancer. On the other hand, the Pu-rich mutation blocked muscle-specific exon exclusion following both inductions. Next, we produced transgenic mice bearing both mutant minigenes and analyzed their splicing patterns in tissues. Based on an analysis of F(1)gamma Pu-del minigene transgenic mice, the purine nucleotide of this element was shown to be necessary for exon inclusion in non-muscle tissue. In contrast, analysis of F(1)gamma Pu-rich minigene mice revealed that the F(1)gamma Pu-rich mutant exon had been excluded from heart and skeletal muscle of these transgenic mice, despite the fact mutation of the exon inhibited muscle-specific exon exclusion in myotubes of early embryonic stage. These results suggested that the splicing regulatory mechanism underlying F(1)gamma pre-mRNA differed between myotubes and myofibers during myogenesis and cardiogenesis.
 ...
PMID:Differential regulation of exonic regulatory elements for muscle-specific alternative splicing during myogenesis and cardiogenesis. 1082 53

Cultured mouse heart-derived myocardial and non-muscle cells were exposed to ethanol, stained with cell-permeant fluorescent vital probes, JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide) and oxidation-sensitive dihydrorhodamine 123, and analyzed by flow cytometry to elucidate ethanol-induced time-wise alterations in the mitochondrial membrane potential (DeltaPsim) and the production of reactive oxygen species (ROS). Ethanol (50 and 200 mM) not only hyperpolarized DeltaPsim of both types of cells but also dose-dependently increased ROS production at 24 h, although a 200-mM dose reduced the production until 3 h. These cell pathophysiological reactions suggest the depression of mitochondrial ATPase and mitochondrial respiratory chain. However, differences between these cells appeared after a 24-h exposure to 200 mM ethanol: the increase in ROS production was approximately twice as large for myocardial cells as for non-muscle cells; and the side-scatter parameter of light scattering significantly increased for myocardial cells, but not for non-muscle cells. All these myocyte-specific alterations indicate an increase in the mitochondrial fraction in a cell. This reaction might be a countermeasure against ethanol-induced dysfunction of mitochondrial respiration that is needed to meet the energy requirements of spontaneous myocardial contractions.
 ...
PMID:Ethanol hyperpolarizes mitochondrial membrane potential and increases mitochondrial fraction in cultured mouse myocardial cells. 1647 59