Increased mRNA levels of Mn-SOD and catalase in embryos of diabetic rats from a malformation-resistant strain

被引:63
作者
Cederberg, J
Galli, J
Luthman, H
Eriksson, UJ
机构
[1] Univ Uppsala, Dept Med Cell Biol, S-75123 Uppsala, Sweden
[2] Karolinska Inst, Karolinska Hosp, Dept Mol Med, Stockholm, Sweden
关键词
D O I
10.2337/diabetes.49.1.101
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Previous studies have suggested that reactive oxygen species (ROS) are mediators in the teratogenic process of diabetic pregnancy. In an animal model for diabetic pregnancy, offspring of the H rat strain show minor dysmorphogenesis when the mother is diabetic, whereas the offspring of diabetic rats of a sister strain, U, display major morphologic malformations. Earlier studies have shown that embryonic catalase activity is higher in the Il than in the U strain, and maternal diabetes increases this difference in activity, The aim of this study was to characterize the influence of genetic predisposition on diabetic embryopathy by comparing the mRNA levels of ROS-metabolizing enzymes in the two strains. We determined the mRNA levels of catalase, glutathione peroxidase, gamma-glutamylcystein-synthetase, glutathione reductase, and superoxide dismutase (CuZn-SOD and Mn-SOD) in day 11 embryos of normal and diabetic H and U rats using semiquantitative reverse transcription-polymerase chain reaction. The mRNA levels of catalase and Mn-SOD were increased in II embryos as a response to maternal diabetes, and no differences were found for the other genes. Sequence analysis of the catalase promoter indicated that the difference in mRNA levels may result from different regulation of transcription. Sequence analysis of the catalase cDNA revealed no differences between the two strains in the translated region, suggesting that the previously observed difference in the electrophoretic mobility in zymograms is due to posttranslational modifications. An impaired expression of scavenging enzymes in response to ROS excess can thus be an integral part of a genetic predisposition to embryonic dysmorphogenesis.
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页码:101 / 107
页数:7
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共 62 条
  • [1] ANDERSON D, 1993, BASIC LIFE SCI, V61, P189
  • [2] [Anonymous], LANCET
  • [3] Outcomes of pregnancy in insulin dependent diabetic women: results of a five year population cohort study
    Casson, IF
    Clarke, CA
    Howard, CV
    McKendrick, O
    Pennycook, S
    Pharoah, POD
    Platt, MJ
    Stanisstreet, M
    vanVelszen, D
    Walkinshaw, S
    [J]. BRITISH MEDICAL JOURNAL, 1997, 315 (7103) : 275 - 278
  • [4] Cederberg J, 1997, TERATOLOGY, V56, P350
  • [5] Free radicals and ethanol-induced cytotoxicity in neural crest cells
    Chen, SY
    Sulik, KK
    [J]. ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 1996, 20 (06) : 1071 - 1076
  • [6] Involvement of hydrogen peroxide in collagen cross-linking by high glucose in vitro and in vivo
    Elgawish, A
    Glomb, M
    Friedlander, M
    Monnier, VM
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (22) : 12964 - 12971
  • [7] TEMPORAL EXPRESSION OF GENES ENCODING FREE-RADICAL METABOLIZING ENZYMES IS ASSOCIATED WITH HIGHER MESSENGER-RNA LEVELS DURING INUTERO DEVELOPMENT IN MICE
    ELHAGE, S
    SINGH, SM
    [J]. DEVELOPMENTAL GENETICS, 1990, 11 (02): : 149 - 159
  • [8] PROTECTION BY FREE OXYGEN RADICAL SCAVENGING ENZYMES AGAINST GLUCOSE-INDUCED EMBRYONIC MALFORMATIONS INVITRO
    ERIKSSON, UJ
    BORG, LAH
    [J]. DIABETOLOGIA, 1991, 34 (05) : 325 - 331
  • [9] DIABETES AND EMBRYONIC MALFORMATIONS - ROLE OF SUBSTRATE-INDUCED FREE-OXYGEN RADICAL PRODUCTION FOR DYSMORPHOGENESIS IN CULTURED RAT EMBRYOS
    ERIKSSON, UJ
    BORG, LAH
    [J]. DIABETES, 1993, 42 (03) : 411 - 419
  • [10] TIMED INTERRUPTION OF INSULIN THERAPY IN DIABETIC BB-E RAT PREGNANCY - EFFECT ON MATERNAL METABOLISM AND FETAL-OUTCOME
    ERIKSSON, UJ
    BONE, AJ
    TURNBULL, DM
    BAIRD, JD
    [J]. ACTA ENDOCRINOLOGICA, 1989, 120 (06): : 800 - 810