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A Salminen

Publications and source records attributed to A Salminen.

At least 73 records · Page 4Linked to original sources
PubMed1991

Selective effects of some anesthetics and detergents on lipid peroxidation of mouse heart homogenates.

1. The effects of some anesthetics and detergents on the Fe2+/ascorbate-stimulated non-enzymatic lipid peroxidation potential and on the NADPH-dependent enzymatic lipid peroxidation capacity were characterized in mouse heart homogenates. 2. Chlorpromazine turned out to be the most efficient inhibitor, causing a 50% inhibition at a concentration of 0.03 mM in the non-enzymatic assay, and at a concentration of 0.02 mM in the enzymatic assay. 3. Tetracaine was about a 10-times weaker inhibitor with IC50-values of 0.25 mM. High concentration of dibucaine (1 mM) exerted a 60% inhibition in the non-enzymatic assay, but lidocaine and procaine had no prominent effect with the concentrations used. 4. In the non-enzymatic, Fe(2+)-stimulated system, a 50% inhibition was obtained by using SDS, Triton X-100, and deoxycholic acid at concentrations of 0.004, 0.03, and 0.15%, respectively. 5. In the NADPH-dependent enzymatic lipid peroxidation system, corresponding concentrations were 0.02, 0.04 and 0.1%. Deoxycholate and Triton X-100 even stimulated (10-20%) the enzymatic lipid peroxidation at the lowest concentrations (0.005-0.01%). Saponin was the least effective of these detergents. 6. It is suggested that anesthetics and detergents induce structural rearrangements in the myocardiac membranes which result in the unavailability of phospholipid substrates to lipid peroxidation.

Anesthetics↗
PubMed1991

Transcription of the muscle regulatory gene Myf4 is regulated by serum components, peptide growth factors and signaling pathways involving G proteins.

The muscle regulatory protein myogenin accumulates in differentiating muscle cells when the culture medium is depleted for serum. To investigate the regulation of myogenin gene expression, we have isolated and characterized the Myf4 gene which encodes the human homologue of murine myogenin. Serum components, basic FGF (b-FGF), transforming growth factor beta (TGF-beta), and EGF, agents which suppress differentiation of muscle cells in vitro, down-regulate the activity of the Myf4 gene, suggesting that it constitutes a nuclear target for the negative control exerted by these factors. The 5' upstream region containing the Myf4 promoter confers activity to a CAT reporter plasmid in C2C12 myotubes but not in fibroblasts and undifferentiated myoblasts. Unidirectional 5' deletions of the promoter sequence reveal that integral of 200 nucleotides upstream of the transcriptional start site are sufficient for cell type-specific expression. The forced expression of the muscle determining factors, MyoD1, Myf5, and Myf6 and to a lesser degree Myf4, results in the transactivation of the Myf4 promoter in C3H mouse 10T1/2 fibroblasts. Pathways potentially involved in conveying signals from the cell-surface receptors to the Myf4 gene were probed with pertussis- and cholera toxin, forskolin, and cAMP. Dibutyryl-cAMP and compounds that stimulate adenylate cyclase inhibit the endogenous Myf4 gene and the Myf4 promoter in CAT and LacZ reporter constructs. Conversely, pertussis toxin which modifies Gi protein stimulates Myf4 gene expression. In summary, our data provide evidence that the muscle-specific expression of the Myf4 gene is subject to negative control by serum components, growth factors and a cAMP-dependent intracellular mechanism. Positive control is exerted by a pertussis toxin-sensitive pathway that presumably involves G proteins.

Adenylate Cyclase Toxin↗
PubMed1991

Implantation of recombinant rat myocytes into adult skeletal muscle: a potential gene therapy.

The ability of skeletal muscle to regenerate provides an excellent therapeutic entry, via genetic engineering, for correcting diseases of skeletal muscle and other tissues. We have used a retrovirus to transfer the cDNA for the human multidrug transporter, encoded by the MDR1 gene, into the genomes of the rat muscle cell line L6 and into primary rat myocytes. The MDR1 gene confers drug resistance to cells, and thus serves as a selectable marker in vitro. In cultured cells, the retroviral promoter-driven human MDR1 cDNA was shown to be stable in the presence or absence of drug selection or muscle cell fusion. MDR1 mRNA was synthesized, as shown by RNA blot analysis and in situ hybridization. The protein product was localized to the plasma membrane of transduced myocytes and myotubes by immunofluorescence. As a model for skeletal muscle gene therapy, transduced L6 myocytes were implanted into the tibialis anterior muscle of Wistar rats. The retroviral sequences of the human MDR1 gene and its mRNA were present in the muscles of Wistar rats 5 days, but not 12 days, after implantation, possibly because of immunorejection. On the other hand, the human MDR1 cDNA was stable in the tibialis anterior muscle of nude mice, which are incapable of immunorejection, at least 4 weeks after implantation of myocytes. Immunosuppression of Wistar rats with cyclosporine A delayed immunorejection of recombinant myocytes, and MDR1 cDNA and mRNA was detected 3-4 weeks after implantation. In situ hybridization revealed that injected recombinant myocytes remain in discrete foci in adult rodent skeletal muscle and express MDR1 mRNA for at least 30 days in nude mice and cyclosporine-treated rats.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Inhibitor studies indicate that active cathepsin L is probably essential to its own processing in cultured fibroblasts.

The lysosomal cysteine proteinase cathepsin L is synthesized in cultured mouse NIH 3T3 cells as a 39 kDa precursor and processed intracellularly into active 29 kDa and 20 kDa + 5 kDa lysosomal forms. Addition to culture media of the peptidyl aldehyde leupeptin, a non-covalent inhibitor of cathepsin L, results in the accumulation of the 20 kDa mature form of the enzyme, resulting in increased activity of cathepsin L as measured in an in vitro assay system in the absence of leupeptin. The more potent irreversible cathepsin L inhibitors benzyloxycarbonyl-Phe-Ala-diazomethane and L-transepoxysuccinyl-L-leucylamino-(4-guanidino)butane, when added to living cells at low concentrations, result in accumulation of all partially processed forms of cathepsin L, especially the 29 kDa form, suggesting that cathepsin L is responsible for its own processing. Exogenous procathepsin L introduced into CHO cells by endocytosis via the mannose 6-phosphate receptor is processed in a manner similar to endogenous procathepsin L. We conclude that the major intracellular pathway for processing of procathepsin L, either endogenous or exogenous, probably requires active cathepsin L.

Animals↗
PubMed1990

Tularemia in children caused by Francisella tularensis biovar palaearctica.

Existing data on tularemia infections in children caused by the biovar Francisella tularensis palaearctica (type B) are limited. The case histories of all patients younger than the age of 16 years in northern Finland who had tularemia, based on the antibody response, during the years 1967 to 1986 are reviewed. A total of 67 children, 28 girls and 39 boys, were identified as having had tularemia. The occurrence of the disease varied greatly among years. Most of the cases occurred in July, August and September. The epidemiology differed significantly from that reported for F. tularensis biovar tularensis (type A). This is most probably attributable to the different vector, which was the mosquito in our series, but the tick in areas where type A is common. There were also clear differences in the clinical picture. The ulceroglandular clinical type was the most common. The clinical symptoms and signs were usually quite benign, but the symptoms lasted for a median duration of 26 days. The patients were treated with different antibiotics and there were no differences in the outcome related to the treatment given. Prospective comparative investigations of antibiotic therapy given for tularemia are needed. It is also important to try to identify which strain is causing the disease in each case.

Adolescent↗
PubMed1990

Lysosomal trafficking in rat cardiac myocytes.

By immunolabeling of cryosections, we have characterized in rat cardiac myocytes the cation-independent mannose-6-phosphate receptor (MPR), a lysosomal membrane glycoprotein, lgp120, and a lysosomal enzyme, MEP (homologous to cathepsin L). Most of the MPR label was located in large membrane-filled structures (MPR structures) in large clusters of mitochondria adjacent to but distinct from the Golgi complex. Lpg120 and MEP showed typical lysosomal localization throughout the cell, often associated with regions that appeared to contain autophagosome-like structures. In addition, MEP and lgp120 co-localized within MPR structures. MEP and MPR were localized inside the lumen of MPR structures. MPR was associated mostly with inner membranes, whereas lgp120 was predominantly bound to the outer limiting membrane. MPR, lgp120, and MEP were not detected in Golgi stacks, but some labeling was seen in the putative TGN. Our data suggest that the MPR structures are prelysosomes involved in lysosomal enzyme targeting in rat cardiac myocytes.

Animals↗
PubMed1989

Increased susceptibility to lipid peroxidation in skeletal muscles of dystrophic hamsters.

The results showed that the total content of lipids, which could be peroxidized with Fe(2 +)/ascorbate stimulation in vitro, was 45.4% and 53.7% higher than normal in the dystrophic hamster muscle at the age of 1 and 3 months, respectively. Correspondingly, the susceptibility to lipid peroxidation (stimulated by ADP-chelated iron at 37 degrees C) was 38.6-74.3% higher in dystrophic muscles. The increases were not related to necrotic lesions and inflammation observed. The activities of glucose-6-phosphate dehydrogenase, glutathione reductase, thioredoxin reductase and catalase were increased in dystrophic muscles but those of superoxide dismutases and glutathione peroxidase were unaffected.

Animals↗
PubMed1989

Enzymatic and nonenzymatic lipid peroxidation capacities and antioxidants in hypoxic and reoxygenated rat myocardium.

The effects of 60 min hypoxia and subsequent reoxygenation for 30 min on enzymatic (NADPH-dependent) and nonenzymatic (Fe2+/ascorbate-induced) lipid peroxidation capacities and on antioxidant levels were studied using Langendorff-perfused rat hearts. The assays were done on the myolayer of the right ventricle (RV) and on the subepi- and subendomyolayers of the left ventricle (epi/endo LV) after normoxic, hypoxic, and reoxygenation phases. The region injured by hypoxia/reoxygenation was located mainly in endo LV, seen as a lesser penetration of the fluorescent dye fluorescein in the myocardium. The electron microscopic findings after reoxygenation revealed swelling of the mitochondria, amorphous mitochondrial structures, and formation of paracrystallines. The myofibrillar structure of the cells was disrupted and the cells showed marked fluid accumulation. Membrane structures were marginated and formed blebs and multilamellar bodies. Ultrastructural changes were most prominent in endo LV, especially after reoxygenation. The increase in leakage of lactate in the perfusate revealed the onset of anaerobic metabolism. Abrupt release of the cytoplasmic enzymes lactate dehydrogenase and creatine kinase at the beginning of the reoxygenation phase suggested cell membrane injury. The capacity for Fe2+/ascorbate-induced lipid peroxidation slightly increased in RV and that for NADPH-dependent, enzymatic lipid peroxidation in endo LV after reoxygenation. Catalase, glutathione peroxidase, and superoxide dismutase activities remained unchanged, whereas glucose-6-phosphate dehydrogenase activity decreased after reoxygenation in RV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The GTP-binding protein Ypt1 is required for transport in vitro: the Golgi apparatus is defective in ypt1 mutants.

The YPT1 gene encodes a raslike, GTP-binding protein that is essential for growth of yeast cells. We show here that mutations in the ypt1 gene disrupt transport of carboxypeptidase Y to the vacuole in vivo and transport of pro-alpha-factor to a site of extensive glycosylation in the Golgi apparatus in vitro. Two different ypt1 mutations result in loss of function of the Golgi complex without affecting the activity of the endoplasmic reticulum or soluble components required for in vitro transport. The function of the mutant Golgi apparatus can be restored by preincubation with wild-type cytosol. The transport defect observed in vitro cannot be overcome by addition of Ca++ to the reaction mixture. We have also established genetic interactions between ypt1 and a subset of the other genes required for transport to and through the Golgi apparatus.

Alleles↗
PubMed1989

The Sec15 protein responds to the function of the GTP binding protein, Sec4, to control vesicular traffic in yeast.

SEC15 function is required at a late stage of the yeast secretory pathway. Duplication of the gene encoding the ras-like, GTP-binding protein, Sec4, can suppress the partial loss of function resulting from the sec15-l mutation, but cannot suppress disruption of sec15. Analysis of the SEC15 gene predicts a hydrophilic protein product of 105 kD. Anti-Sec15 antibody recognizes a protein of 116-kD apparent molecular mass which is associated with a microsomal fraction of yeast in a strongly pH dependent fashion. Overproduction of Sec15 protein interferes with the secretory pathway, resulting in the formation of a cluster of secretory vesicles, and a patch of Sec15 protein revealed by immunofluorescence. The sec4-8 and sec2-4l mutations, but not mutations in other SEC genes, prevent formation of the Sec15 protein patch. We propose that Sec15 protein responds to the function of the Sec4 protein to control vesicular traffic.

Amino Acid Sequence↗
PubMed1989

Decreased level of cardiac antioxidants in endurance-trained rats.

Han-Wistar rats were exposed to a 194-200 h swimming protocol which caused a significant increase in the cardiac weight. The levels of various tissue antioxidants were assayed from the myocardium of the right ventricle and from the left ventricle (subendo- and subepimyocardium). This endurance training decreased the activities of catalase in the right ventricle and in the subendo- and subepimyocardium and Cu,Zn-superoxide dismutase in the subendomyocardium as well as the concentration of vitamin E in the right ventricle and in the subendomyocardium. Also, the activity of thioredoxin reductase decreased in each part of myocardium and that of glutathione reductase in the right ventricle and in the subepimyocardium. The activity of glucose-6-phosphate dehydrogenase increased in the right ventricle and in the subepimyocardium. The activity of glutathione peroxidase and the total tissue contents of carnosine and anserine and tissue sulphydryl groups remained unchanged as compared to the control group. The endurance training caused only minor changes in the regional distribution of antioxidants. The major findings were the disappearance of the difference in the activity of catalase between the right and the left ventricle and the increase in the activity of glucose-6-phosphate dehydrogenase as compared to that of the left ventricle. The results show that endurance training by swimming decreases the level of cardiac antioxidants. This decrease may be due to the increased oxygen metabolism and the subsequent increase in the formation of oxygen free radicals, which could deplete the antioxidant pool.

Animals↗
PubMed1988

A GTP-binding protein required for secretion rapidly associates with secretory vesicles and the plasma membrane in yeast.

SEC4, one of the 10 genes involved in the final stage of the yeast secretory pathway, encodes a ras-like, GTP-binding protein. In wild-type cells, Sec4 protein is located on the cytoplasmic face of both the plasma membrane and the secretory vesicles in transit to the cell surface. In all post-Golgi blocked sec mutants, Sec4p is predominantly associated with the secretory vesicles that accumulate as a result of the secretory block. Sec4p is synthesized as a soluble protein that rapidly (t1/2 less than or equal to 1 min) and tightly associates with secretory vesicles and the plasma membrane by virtue of a conformational change of a covalent modification. These data suggest that Sec4p may function as a "G" protein on the vesicle surface to transduce an intracellular signal needed to regulate transport between the Golgi apparatus and the plasma membrane.

Cell Membrane↗
PubMed1988

X-linked myopathy with excessive autophagy: a new hereditary muscle disease.

We report on 3 brothers with a myopathy that also affected their maternal grandfather and great-uncle. Characteristic features are onset in early childhood, very slow progression, normal life expectancy, weakness of proximal limb muscles, especially in the legs, elevation of serum creatine kinase, and no cardiac or intellectual involvement. In biopsy material muscle fibers are almost never necrotic but show excessive autophagic activity and exocytosis of the phagocytosed material. We suggest that this family has an undescribed type of congenital myopathy, for which we propose the name X-linked myopathy with excessive autophagy.

Adult↗
PubMed1988

Food deprivation decreases the exertion-induced acid hydrolase response in mouse skeletal muscle.

Strenuous prolonged running causes muscle fibre necrosis in skeletal muscles. The muscle injury is associated with inflammation and a strong increase in the total activities of certain acid hydrolases a few days after exertion. The activity changes of acid hydrolases quantitatively well reflect the severity of histopathological changes during the myopathy (for review see Salminen, Acta Physiol Scand [Suppl 539] 1985). In this study male NMRI-mice were exposed to a protocol of fasting and refeeding together with or without a 6 h run on a treadmill at 13.5 m.min-1. The animals were killed 4 days after the exercise and samples from the red part of quadriceps femoris were analyzed for arylsulfatase (ASase) and beta-glucuronidase (GUase) activities. Starvation protocols did not affect ASase or GUase. Running caused a 3.2-fold increase in ASase and a 5.1-fold increase in GUase. If mice were exercised in the fasted condition a normal exercise response occurred in both activities, but when mice were exercised 2 days after the finish of fasting the exercise response was greatly diminished. Thus food deprivation followed by 2 days refeeding induces a protection against exercise myopathy in mice. The protection greatly resembles that induced by regular endurance training preceding strenuous prolonged exertion.

Animals↗
PubMed1988

Age- and sex-related differences in lipid peroxidation of mouse cardiac and skeletal muscles.

1. The purpose of the present study was to characterize age- and sex-related changes in lipid peroxidation capacities and enzymatic antioxidants of cardiac and skeletal muscles in NMRI-mice (Mus musculus). 2. Lipid peroxidation rates (unstimulated and enzymatic/iron-stimulated) strongly decreased in skeletal muscle during ageing. 3. Unstimulated lipid peroxidation rate but not that of stimulated, also decreased in cardiac muscle. 4. The total level of Fe2+/ascorbate-stimulated non-enzymatic lipid peroxidation was not, however, affected by ageing. 5. The activity of catalase slightly increased in cardiac muscle and that of glutathione peroxidase in skeletal muscle during ageing. 6. Unstimulated lipid peroxidation rate was significantly higher in the skeletal muscle of male than female mice. 7. Correspondingly, the Fe2+/ascorbate-stimulated lipid peroxidation capacities of microsomal and mitochondrial fractions of skeletal muscle were significantly higher in male mice. 8. The activity of glutathione peroxidase as well as the concentration of lipofuscin were higher in the cardiac muscles of female than male mice.

Aging↗