Search PubMed⌕ Search

Biomedical subjects

K W Wahle

Publications and source records attributed to K W Wahle.

At least 19 recordsLinked to original sources
PubMed2001

Fatty acid regulation of protein kinase C isoforms in prostate cancer cells.

Polyunsaturated fatty acids influence the aetiology of prostate cancer. Their effects on cellular mechanisms regulating prostate tumorigenesis are unclear. Using prostate cancer cells (LNCaP), we determined effects of n-9-OA, n-6-LA, and n-3-EPA on total PKC and its isoforms in relation to cell proliferation and PSA production. PKC-alpha, delta, gamma, iota, mu, and zeta were present in LNCaP cells; PKC-beta, epsilon, eta, and theta isoforms were not. PKC-alpha was detected only in cytosol; PKC-delta, iota, gamma, and mu were present in cytosol and in membranes. Fatty acids increased cell proliferation, total PKC activity and elicited pro-proliferative effects on specific PKC isoforms (PKC-delta and -iota). EPA and LA increased total PKC activity and reduced membrane-abundance of PKC-delta. OA reduced cytosolic and membrane PKC-delta. Only EPA reduced PKC-gamma membrane abundance. Fatty acids enhanced cytosolic PKC-iota abundance but only EPA and to a lesser extent LA increased its membrane content. Changes in PKC-delta, -iota, and -gamma did not affect PSA production.

Cell Division↗
PubMed1999

The effect of increased intakes of polyunsaturated fatty acids and vitamin E on DNA damage in human lymphocytes.

The effect of increasing dietary intakes of polyunsaturated fatty acids (PUFAs) and vitamin E on indices of oxidative DNA damage was investigated. Twenty-one healthy male, nonsmokers aged 28.9 +/- 1.3 years participated in a free-living, split plot/change over trial in which half the volunteers consumed diets containing 5% PUFA as food energy for 4 wk and, after a 10 wk washout period, consumed a 15% PUFA diet for another 4 wk. The other volunteers followed an identical protocol, except that they consumed the 15% PUFA diet first. The diets were provided to volunteers either with or without an additional 80 mg dalpha-tocopherol acetate/day; otherwise total fat, carbohydrates, protein, and basal vitamin E contents remained unchanged. DNA damage induced by 200 microM H(2)O(2) in lymphocytes from volunteers as well as endogenous DNA damage in the form of oxidized pyrimidines, measured by alkaline single-cell gel electrophoresis (the comet assay), significantly decreased after consumption of the 5% PUFA diet (P<0.001 and P=0.01, respectively), but significantly increased after consumption of the 15% PUFA diet when alpha-tocopherol levels were in the range of 5-7 mg/day (P=0. 008 and P=0.03, respectively). These changes were abolished by an additional 80 mg dalpha-tocopherol/day. This study indicates that increasing dietary levels of PUFA to 15% may adversely affect some indices of DNA stability. However, increasing the dietary intake of vitamin E by 80 mg/day ameliorates the damaging effects of PUFA. -Jenkinson, A. McE., Collins, A. R., Duthie, S. J., Wahle, K. W. J., Duthie, G. G. The effect of increased intakes of polyunsaturated fatty acids and vitamin E on DNA damage in human lymphocytes.

Adult↗
PubMed1999

Fatty acids and endothelial cell function: regulation of adhesion molecule and redox enzyme expression.

Different types of dietary fatty acids have distinct, and sometimes opposing, effects on endothelial cell function. Long-chain n-3 polyunsaturated fatty acids from fish oil (eicosapentaenoic-acid-20:5n-3 and docosahexaenoic-acid-22:6n-3) attenuate cytokine-induced adhesion molecule expression (mRNA and protein) while the n-6 polyunsaturated fatty acid arachidonic acid (eicosatetraenoic-acid-20:4n-6) either has no effect, or elicits as up- or down-regulation. Conjugated linoleic acids derived from 18:2n-6, linoleic acid also reduced the expression of adhesion molecules. These polyunsaturated fatty acids also induced redox enzyme expression (mRNA and protein) in endothelial cells and modulation of redox-sensitive transcription factors (e.g. nuclear factor kappa B, activated protein-1) which regulate the gene expression of adhesion molecules, redox enzymes and various stress proteins. The induction of redox enzyme expression by n-3 polyunsaturated fatty acids and conjugated linoleic acids could explain their inhibitory effects on gene transcription and adhesion molecule protein expression. Individual adhesion molecule genes and transcription factors appear to differ in their responsiveness to various oxidant stimuli and non-redox, more direct regulatory mechanisms (e.g. peroxisome proliferator activation receptor activation) might also be involved in their regulation.

Animals↗
PubMed1999

Fatty acids and prostate cancer: current status and future challenges.

In this article the basic biology and function of fatty acids (FAs) will be reviewed. The literature relating to FAs and prostate cancer will be evaluated and possible mechanisms for the mode of action of FAs in the carcinogenesis and progression of prostate cancer will be discussed. In addition, the potential role for specific FAs in the treatment and prevention of prostate cancer will be assessed.

Animals↗
PubMed1996

Modulation of glutathione peroxidase activity in human vascular endothelial cells by fatty acids and the cytokine interleukin-1 beta.

Objectives of this study were (a) to assess the extent of oxidative stress elicited in human endothelial cells by n-3, n-6 and n-9 mono- and polyunsaturated fatty acids and by interleukin-1 beta and (b) to determine how such stress influenced glutathione peroxidase (GSHPx) activity. Fatty acids were co-incubated with human vascular endothelial cells (HUVEC) for 24 h. Lipid peroxidation, monitored as conjugated diene (CD) formation, increased 3-4-fold with increasing eicosapentaenoic and docosahexaenoic acids: 2-3-fold with linoleic acid; decreased by 50% with arachidonic acid and was unchanged with oleic acid. Changes in glutathione peroxidase activity mirrored conjugated diene formation in the HUVEC incubated with fatty acids. Interleukin-1 beta also increased glutathione peroxidase and conjugated diene formation; the latter increased enzyme activity dose-dependently suggesting a possible role for this oxidation product in the induction of glutathione peroxidase activity. The ability of fish oil fatty acids to induce antioxidant enzymes, particularly those of the glutathione redox system, may be an important mechanism protecting cells and tissues against oxidative and inflammatory cytokine elicited damage.

Arachidonic Acid↗
PubMed1996

Effects of isomeric cis and trans eighteen carbon monounsaturated fatty acids on porcine platelet function.

The effects of different positional cis and trans isomers (9, 11, 12 and 13) of C(18) monoenoic fatty acids on the response of porcine platelets to collagen and thrombin stimulation were determined. Cis isomers inhibited aggregation in response to 2 microgram/ml or 5 microgram/ml collagen and 0.1 U/ml of thrombin with almost equal effectiveness, with the exception of the 9- and 11-isomers which gave reduced inhibition of aggregation with thrombin and collagen stimulation respectively. All cis isomers inhibited TXA(2) formation (determined as TXB(2)) elicited by collagen with almost equal effectiveness. Trans isomers were less effective than cis in inhibiting collagen induced aggregation particularly at the higher collagen concentrations. Inhibition of TXB(2) formation was less marked with trans isomers but a clear dissociation between the extent of inhibition of aggregation and TXB(2) formation was evident. Cis isomers also inhibited aggregation in response to 0.1 U/ml thrombin whereas trans isomers augmented aggregation but still reduced TXB(2) formation. Isomers did not elicit their effects through incorporation into platelet membrane phospholipids. Aggregation studies were carried out using the impedance method which is more sensitive than the optical method hitherto described, particularly for lipid studies.

Animals↗
PubMed1996

Inhibitory effect of fish oil N-3 polyunsaturated fatty acids on the expression of endothelial cell adhesion molecules.

A rapid, cost-effective and sensitive method of Northern analysis using specific oligonucleotide probes combined with chemiluminescence was used to detect adhesion molecule transcripts with as little as 50 ng of total RNA from activated primary human umbilical vein endothelial cells (HUVEC). Activation of cultured HUVEC with the inflammatory cytokine interleukin 1beta (IL-1beta) resulted in distinct time- and dose-dependent patterns of expression of ICAM-1, E-Selectin and VCAM-1 transcripts. The levels of all three transcripts were maximal after 2.5 hours of stimulation with IL-1beta. However, the upregulation of ICAM-1 mRNA levels in response to IL-1beta was much more stable than the transient induction of E-selectin and VCAM-1 transcripts. In addition, we have found that eicosapentaenoic acid (EPA) and docosapentaenoic acid (DHA) omega3 fatty acids that have been reported to modulate the adhesive properties of cells involved in immune/inflammatory responses do not affect the expression of ICAM-1, VCAM-1 or E-selectin in resting HUVEC. However, EPA (65 microM) or DHA (65 microM) do attenuate the induction of each of these adhesion molecules in IL-1beta-activated HUVEC.

Blotting, Northern↗