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Biomedical subjects

K W Wahle

Publications and source records attributed to K W Wahle.

At least 19 recordsLinked to original sources
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↗
PubMed1995

Decreased phospholipid polyunsaturated fatty acid content and superoxide dismutase activity in cardiac muscle of malignant hyperthermia-susceptible swine.

Homogenates of cardiac left ventricle from malignant hyperthermia-susceptible (MHS) pigs produced a circa 72% more pentane than those from malignant hyperthermia-resistant (MHR) animals, indicating enhanced peroxidation of n-6 fatty acids. This is consistent with the observed circa 70% decrease in total phospholipid polyunsaturated fatty acids (PUFA) in MHS compared with MHR tissue, a decrease mainly due to the quantitatively greater loss of n-6 PUFA. Although the percentage loss of n-3 PUFA was greater than that of n-6 PUFA (90% vs 60%), absolute amounts were insufficient to register as ethane production. Three-fold greater phospholipid content of MHS compared with MHR ventricles indicates reduced neutral lipid content probably due to increased catecholamine stimulation. These findings were associated with a small but significant decrease in superoxide dismutase activity in MHS tissues.

Animals↗
PubMed1994

Arachidonic acid metabolism in benign and malignant prostatic tissue in vitro: effects of fatty acids and cyclooxygenase inhibitors.

Concentrations of fatty acids (FA) in prostatic tissue of patients with either benign or malignant prostatic disease have previously been shown to be significantly different. In particular, there was a significant reduction in arachidonic acid (AA, C20:4n-6) and docosapentaenoic acid (DPA, C22:5n-6) concentrations in malignant prostatic tissue (PCa) phospholipids (PL). It was suggested that the decreased AA concentration in PCa may be due to its increased metabolism via the cyclooxygenase (CO) and/or lipoxygenase (LO) pathways to produce eicosanoids such as prostaglandins (PGs) and/or leukotrienes (LTs) rather than an impairment in desaturase activity in situ. The eicosanoid production in benign prostatic tissue (BPH) and PCa was determined using [3H]AA. The only eicosanoid produced in significant amounts by either tissue was PGE2 and PCa converted radiolabelled AA to PGE2 at an almost 10-fold higher rate than BPH. PGE2 production from [3H]AA by PCa was investigated in the presence of oleic acid (OA, C18:1n-9), eicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA, C22:6n-3), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosatetraynoic acid (ETYA) and ketoprofen (KPN) respectively. OA was found to be the most effective inhibitor of PGE2 production by PCa compared with DHA, EPA, ETYA and KPN, while DGLA was the least effective. Diacylglycerol (DAG) formation from labelled AA by PCa was about 4-fold greater than in BPH. Such high levels of DAG may be a means of promoting tumorigenesis through activation of protein kinase C as found with phorbol esters which can be regarded as DAG analogues.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1994

Effect of dietary lipids and endocrine changes on polyunsaturated fatty acids in phospholipids of pancreas and brown adipose tissue of obese and lean rats.

Obese (fa/fa) rats fed on control diet have lower proportions of linoleic acid (18:2n-6) and/or arachidonic acid (20:4n6) in IBAT and pancreas phospholipids compared with lean (Fa/-) rats. Lower stearic acid (18:0) to oleic acid (18:1n-9) mean ratios in fa/fa compared with Fa/- suggest enhanced delta 9-desaturase activity in the former. 18:2/20:4 mean ratios in pancreas, but not IBAT, are indicative of a reduced delta 6-desaturase activity in fa/fa rats. Absolute amounts of phospholipids (mg/unit tissue wt) were 2-fold greater in IBAT of fa/fa compared with Fa/- rats, irrespective of their diet. This was reflected in greater absolute amounts of 18:2n-6 and 20:4n-6 only in HSO and HTO fa/fa groups, but not in the control group. Adrenalectomy (Adx) or T3 treatment also modified phospholipid fatty acid composition of IBAT and pancreas phospholipids in animals fed on the control diet with fa/fa rats more sensitive to endocrine induced changes. In fa/fa rats T3 treatment increased docosahexaenoic acid (22:6n-3) in IBAT of both phenotypes compared with the control, but this effect was evident only in fa/fa and not Fa/- pancreas. T3 treatment also increased docosapentaenoic acid (22:5n-3) in IBAT from, both phenotypes, but no 22:5n-3 was evident in the pancreatic tissue of these animals. ADX also increased 22:6n-3 in the IBAT of fa/fa (Fa/- values were less than 1%) but not in the pancreas of fa/fa or Fa/-. ADX modified the relative proportions of 18:0 to 18:1 and 18:2 to 20:4 in IBAT and pancreas of fa/fa in a way that indicated decreased delta 9-desaturase and increased delta 6-desaturase activities; these effects tended toward normal again in pancreas of fa/fa rats on corticosterone replacement (CST).

Adipose Tissue, Brown↗
PubMed1992

Lipid peroxidation, antioxidant concentrations, and fatty acid contents of muscle tissue from malignant hyperthermia-susceptible swine.

Homogenates of semitendinosus muscle from malignant hyperthermia (MH)-susceptible pigs produced threefold more pentane than those from MH-resistant pigs, indicating enhanced free radical-mediated peroxidation of n-6 fatty acids. This did not reflect a deficiency in tissue antioxidants or antioxidant-enzymes but glutathione concentrations and glutathione peroxidase activities were increased in the tissue from MH-susceptible swine, consistent with an adaptive response to a sustained oxidant stress. A lower proportion of linoleic acid (18:2 n-6) in phospholipids and neutral lipids in muscle from MHS pigs indicated increased peroxidation or metabolism (desaturation and elongation). The increased oleic acid (18:1 n-9) in the MHS muscle indicated that desaturase activity was elevated in all lipid classes. The results are consistent with the hypothesis that enhanced free radical activity and lipid peroxidation contributes to the abnormalities in Ca2+ homeostasis and polyunsaturated fatty acid metabolism in MH.

Animals↗
PubMed1992

Altered platelet stearic to oleic acid ratio in malignancy.

Alteration of lipid metabolism associated with malignant disease is well-documented and some studies have suggested a reduced stearic to oleic acid ratio occurs in erythrocytes in cancer patients. In this study, the fatty acid composition was measured in platelets, which are capable of lipid synthesis and have a much shorter lifespan. While demonstrating any malignancy related change in the platelet stearic to oleic acid ratio the study aimed to assess whether it could be of value as a tumour marker. Patients with active malignancy (n = 46) had a lower ratio of stearic to oleic acid than those with malignant disease in clinical remission [mean (S.D.) 1.08 (0.22) vs. 1.26 (0.30), P less than 0.01], and 22 healthy controls [1.29 (0.24), P less than 0.001]. However in a group of 17 patients with chronic, non-malignant diseases the ratio was also lower than in normal controls and similar to that seen in the active malignancy group [0.97 (0.29)]. Thus while a reduction in platelet stearic to oleic acid ratio was found in active malignancy, it is not specific to neoplastic disease.

Adolescent↗