A L Yaktine

Iowa State University, Ames, IA, United States

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Publications (7)32.76 Total impact

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    ABSTRACT: The aim of this study was to determine the effects of 40% dietary energy restriction (DER) relative to ad libitum feeding on AP-1-DNA binding and expression of c-Jun protein and c-jun mRNA in SENCAR mouse skin treated with acetone or 12-O-tetradecanoylphorbol 13-acetate (TPA). The role of the glucocorticoid hormone corticosterone (CCS) was investigated by adding CCS or vehicle control to the drinking water of adrenalectomized mice. AP-1-DNA binding, measured by electrophoretic mobility shift assay, showed that TPA treatment for 4 h increased AP-1-DNA binding by 2-fold over acetone controls (P < 0.05) and that DER reduced basal and TPA-induced AP-1-DNA binding in comparison with ad libitum fed groups in sham-operated mice (P < 0.05). TPA treatment increased c-Jun protein levels in control fed mice (4-fold) and in DER mice (2-fold) over basal levels 4 h post-treatment (P < 0.05). Analyzed over all groups, DER reduced c-Jun protein levels (P < 0.01) and this effect was reversed by adrenalectomy. TPA induction of c-jun mRNA was also reduced by DER compared with ad libitum fed mice (P < 0.05). Adrenalectomy and CCS supplementation demonstrated that the effects of DER on AP-1-DNA binding were mediated in part by CCS. Measurement of blood plasma CCS concentrations showed that: (i) DER increased CCS 5-fold over ad libitum fed mice in sham-operated animals (P < 0.05); (ii) adrenalectomy decreased CCS over sham-operated mice (P < 0.05); (iii) TPA treatment had no effect on CCS. Blood plasma IGF-I concentrations were unaffected by CCS modulation or TPA treatment but were decreased by DER compared with ad libitum fed mice (P < 0.05). Thus, dietary energy restriction may inhibit cancer mechanistically by reducing overall AP-1 transcription through a process that is mediated in part by glucocorticoid hormones.
    Carcinogenesis 09/2001; 22(9):1421-7. · 5.64 Impact Factor
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    D F Birt, E Duysen, W Wang, A Yaktine
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    ABSTRACT: Previous research in this laboratory demonstrated elevated plasma corticosterone and reduced protein kinase C (PKC) activity and selective isoform expression in the epidermis of dietary energy-restricted mice. Because PKC is implicated in skin carcinogenesis and because both energy restriction and glucocorticoid hormone inhibit skin carcinogenesis, the purpose of the present research was to determine whether the elevated glucocorticoid hormone in the energy-restricted mouse contributed to the changes in PKC protein expression. Two strategies were used to control corticosterone in adrenalectomized mice: (a) corticosterone-containing pellets were implanted in mice, and a dose response increase in corticosterone was observed with 5-, 10-, and 35-mg corticosterone implants with average peak values of 68 +/- 22 ng/ml (P < 0.01); and (b) corticosterone was administered in the drinking water, and plasma corticosterone was elevated in a dose-dependent manner in mice killed at 6:00-6:30 p.m. (P < 0.01; peak values of 300-400 ng/ml). The expression of PKCalpha, PKCdelta, and PKCepsilon protein were not consistently altered by corticosterone with the two strategies. PKCeta protein expression was elevated in the adrenalectomized mice administered 3 or 60 microg of corticosterone/ml in drinking water (P < 0.01). PKCzeta protein expression was reduced by all doses of corticosterone in the implant or drinking water (P < 0.05), and a reduction of 41% was achieved with the mice administered 60 microg of corticosterone/ml in drinking water. In mice fed control or energy-restricted diet, with or without adrenalectomy, PKCzeta protein was reduced in sham-operated, energy-restricted mice in comparison with control diet, sham-operated mice (P < 0.02), whereas PKCzeta protein was not significantly different between adrenalectomized control and adrenalectomized, energy-restricted mice. These data indicate that administration of corticosterone in drinking water most closely mimicked the circulating corticosterone and epidermal PKC changes observed in dietary energy restriction. Elevated plasma glucocorticoid levels in the dietary energy-restricted mouse may contribute to the alteration of PKC protein levels in the epidermis.
    Cancer Epidemiology Biomarkers &amp Prevention 06/2001; 10(6):679-85. · 4.56 Impact Factor
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    Y Liu, E Duysen, A L Yaktine, A Au, W Wang, D F Birt
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    ABSTRACT: Ongoing studies in our laboratory have demonstrated that dietary energy restriction (DER) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced AP-1 transcription factor binding to DNA in the epidermis of SENCAR mice. To dissect the specific signal transduction pathways through which DER inhibits the AP-1:DNA binding, we analyzed the activities of three major MAP kinases that lead to the induction of AP-1. The changes in ERK1 and ERK2 protein expression and phosphorylation were further characterized by western blot analysis. Female SENCAR mice were pre-fed ad libitum (AL) or 40% DER diet for 8-10 weeks. The kinase activities in mouse epidermis were determined by immune complex kinase assays at 0.5, 1, 4, or 6 h following treatment with 3.2 nmol TPA to the shaved dorsal backs. ERK activity at 1 h post-TPA treatment was nearly 5-fold (P< 0.005) above basal levels in AL mice while the increase was abolished in DER mice. The TPA-induced ERK activity in AL mice was accompanied by increased phosphorylation of ERK1 and ERK2 (P< 0.05), which was abrogated in DER mice. In addition, DER mice exhibited reduced expression of total ERK1 and ERK2 and higher proportions of ERK1 and ERK2 phosphorylation in comparison with AL mice (P<0.05). JNK activity was decreased at 1 and 6 h but increased at 4 h (P<0.05) post-TPA treatment. TPA did not change p38 kinase activity at the time points tested. Neither JNK nor p38 activity was altered by DER. Taken together, our results indicated for the first time that DER blocked the TPA stimulation of ERK activity and suggested that the inhibition of TPA-induced AP-1 activity by DER is likely through inhibition of ERK but not JNK or p38 kinase pathway.
    Carcinogenesis 04/2001; 22(4):607-12. · 5.64 Impact Factor
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    D F Birt, A Yaktine, E Duysen
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    ABSTRACT: Dietary energy restriction (DER) inhibits carcinogenesis in numerous animal models. DER is a potent and reproducible inhibitor of two-stage mouse skin carcinogenesis when administered during the promotion phase. Previous research demonstrated that adrenalectomy abolished cancer prevention by food restriction. Several lines of evidence suggest that glucocorticoid elevation in the DER mouse mediates the prevention of skin cancer. Our research tested the hypothesis that elevated glucocorticoid hormone activates the glucocorticoid receptor (GR) and that this activated receptor interferes with the activator protein-1 (AP-1) transcription factor. Induction of AP-1 by the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) is essential to tumor promotion. We have been unable to demonstrate elevated activated GR in the epidermis of the DER mouse, perhaps because only indirect strategies have been possible with the use of epidermis from DER mice. However, DER blocked the induction of AP-1 and c-jun, a constituent protein of AP-1, in the epidermis of mice. Current studies are focused on the inhibition of signaling down the MAP-1/Raf-1 kinase pathway that leads to induction of constituent proteins of AP-1, including c-Jun. Although several pathways lead to the induction of AP-1 transcriptional activity, the MAP-1/Raf-1 pathway can be activated by protein kinase C (PKC); previous studies from our laboratory demonstrated an inhibition of PKC activity and a reduction in selected isoforms of PKC in the epidermis of the DER mouse. Our current working hypothesis is that elevated glucocorticoid hormone in the DER mouse reduces the amount and activity of PKC isoforms important in the activation of MAP-1/Raf-1 kinase pathway. We propose that this results in attenuation in the induction of the AP-1 transcription factor by TPA. Because AP-1 induction by TPA is obligatory for mouse skin promotion, we propose this as an essential component of the mechanism of DER prevention of mouse skin carcinogenesis.
    Journal of Nutrition 03/1999; 129(2S Suppl):571S-574S. · 4.20 Impact Factor
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    ABSTRACT: The purpose of this study was to demonstrate that dietary energy restriction elevates plasma glucocorticoid hormone (GCH) levels while maintaining a circadian profile. Furthermore, we indirectly measured the effect of energy restriction on receptor activation in epidermis by determining the cellular localization of receptor protein in control-fed and energy-restricted (ER) mice. SENCAR mice were maintained on an ad libitum control diet or an ER diet that provided 60% of the total energy consumed by control-fed mice. Plasma corticosterone levels were determined by radioimmunoassay. Glucocorticoid receptor (GR) protein levels in epidermal lysates were measured by western blotting. Electron microscopy was used to identify gold-conjugated immunoreactive GR in epidermal cells of the skin in control and ER mice. Plasma corticosterone levels in ER mice were significantly increased 10 times over the levels in control mice at 0700 h, significantly increased two times over control levels at 1600 h, and not different from controls at 2300 h in the circadian cycle. The total amount of epidermal GR protein in ER mice was 140% (95% confidence interval, 104-169%) of that in controls at the early time point, not different at the midpoint, and 60% (95% confidence interval, 48-79%) of that in controls at the late time point. The distribution of gold-conjugated GR in the cytoplasmic and nuclear compartments of epidermal cells was similar in control and ER mice. Thus, we showed that dietary ER increased the level of plasma GCH without abolishing diurnal variation. However, an increase in ligand activation in epidermal cells, as indicated by nuclear localization of GR protein, was not supported by the results of this study.
    Molecular Carcinogenesis 02/1998; 21(1):62-9. · 4.27 Impact Factor
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    ABSTRACT: Dietary restriction in experimental animals enhances life span, delays disease, inhibits immunological perturbations, and ameliorates cancer. Protein kinase C (PKC) isozymes mediate signals generated by hormones, growth factors, and neurotransmitters for cell proliferation and differentiation. The results of our study showed that a C-terminally directed anti-PKC zeta antibody detected an 81-kDa band in the pancreases of control and energy-restricted hamsters. Syrian golden hamsters were fed energy-restricted diets formulated such that the hamsters received 90% (10% energy restriction (ER)), 80% (20% ER), or 60% (40% ER) of the total energy consumed by control hamsters, with the energy reduced proportionally from fat and carbohydrate. ER decreased PKC zeta isozyme levels by 40-75% in hamsters fed 10, 20, and 40% ER diets for 8 wk. PKC zeta isozyme expression was decreased by 75-80% in hamsters fed ER diets for 15 wk. Although ER caused significant decreases in PKC zeta isozyme levels compared with those of control hamsters at both time points, the relative differences in PKC zeta levels between the dietary ER groups (10, 20, and 40%) were small and not significant. A significant decrease in the body weights of ER animals compared with those of controls was observed at both time points. No differences in tomato lectin and phytohemagglutinin reactivity were observed between control animals and animals fed 10, 20, and 40% ER diets. Furthermore, the cellular expression of PKC zeta in the hamster pancreas did not differ among hamsters fed the various ER diets. These observations may be important for understanding not only the role of dietary ER in pancreatic cancers but also PKC zeta signal transduction mechanisms in normal pancreatic physiology.
    Molecular Carcinogenesis 10/1995; 14(1):10-5. · 4.27 Impact Factor
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    ABSTRACT: Female SENCAR mice were pre-fed a control or 40% energy-restricted (ER) diet with energy removed from fat and carbohydrate, or a control, balanced high fat (BHF, with similar energy from fat and carbohydrate), 35% energy restricted from fat (HCR) or 35% energy restricted from carbohydrate (HFR) diet. Epidermal cells were isolated by trypsin digestion for measurement of protein kinase C (PKC) activity, lipid composition or lipid metabolism. Dietary restriction of fat or carbohydrate energy (HFR or HCR group) reduced particulate PKC activity in epidermal cells compared with cells from control mice. The ratio of soluble particulate PKC activity was higher in epidermal cells from mice fed the HCR diet compared with those fed the HFR diet. Diet did not affect soluble PKC activity. Inositol accumulation was measured in the water- or lipid-soluble fractions of prelabeled ([3H]inositol) epidermal cells following a 1-h incubation in media with LiCl. Phosphatidylinositol, inositol biphosphate and inositol triphosphate fractions were more heavily labeled in cells from mice fed the ER diet. Energy restriction did not modify epidermal total lipid or phospholipid composition, but 1,2-diacylglycerol levels were elevated in relation to cell number in epidermal cells from mice fed the ER diet. These data suggest that dietary energy restriction modified PKC activity through a pathway other than alteration in membrane lipid composition or inositol lipid metabolism.
    Journal of Nutrition 05/1994; 124(4):485-92. · 4.20 Impact Factor

Publication Stats

77 Citations
32.76 Total Impact Points

Institutions

  • 2001
    • Iowa State University
      • Department of Food Science and Human Nutrition
      Ames, IA, United States
  • 1995–1998
    • University of Nebraska Medical Center
      Omaha, Nebraska, United States
  • 1994–1998
    • University of Nebraska at Omaha
      • • Eppley Institute for Research in Cancer and Allied Diseases
      • • Department of Biochemistry and Molecular Biology
      Omaha, NE, United States