ABSTRACT
An N-acetyl sugar-binding lectin (termed iNoL) displaying cytotoxic activity against human cancer cells was isolated from the slipper lobster Ibacus novemdentatus (family Scyllaridae). iNoL recognized monosaccharides containing N-acetyl group, and glycoproteins (e.g., BSM) containing oligosaccharides with N-acetyl sugar. iNoL was composed of five subunits (330, 260, 200, 140, and 30 kDa), which in turn consisted of 70-, 40-, and 30-kDa polypeptides held together by disulfide bonds. Electron microscopic observations and gel permeation chromatography indicated that iNoL was a huge (500-kDa) molecule and had a polygonal structure under physiological conditions. iNoL displayed cytotoxic (apoptotic) effects against human cancer cell lines MCF7 and T47D (breast), HeLa (ovarian), and Caco2 (colonic), through incorporation (internalization) into cells. The lectin was transported into lysosomes via endosomes. Its cytotoxic effect and incorporation into cells were inhibited by the co-presence of N-acetyl-D-mannosamine (ManNAc). Treatment of HeLa cells with iNoL resulted in DNA fragmentation and chromatin condensation, through activation of caspase-9 and -3. In summary, the novel crustacean lectin iNoL is incorporated into mammalian cancer cells through glycoconjugate interaction, and has cytotoxic (apoptotic) effects.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Decapoda/chemistry , Endocytosis , Lectins/pharmacology , Animals , Antineoplastic Agents/chemistry , Caco-2 Cells , Caspase 3/metabolism , Caspase 9/metabolism , Endosomes/drug effects , Endosomes/metabolism , Glycoproteins/metabolism , HeLa Cells , Humans , Lectins/chemistry , Lectins/toxicity , Lysosomes/drug effects , Lysosomes/metabolism , MCF-7 Cells , Protein BindingABSTRACT
AIM: Physical exercise reduces obesity, insulin resistance and dyslipidemia. We previously found that maternal obesity alters central appetite circuits and contributes to increased adiposity, glucose intolerance and metabolic disease in offspring. Here we hypothesized that voluntary exercise would ameliorate the adverse metabolic effects of maternal obesity on offspring. METHODS AND RESULTS: Sprague-Dawley females fed chow (C) or high-fat diet HFD (H) were mated. Female offspring from C dams were weaned onto chow (CC); those from H dams recieved chow (HC) or HFD (HH). Half of each group was provided with running wheels (CC(EX), HC(EX), HH(EX); n=10-12). Maternal obesity increased body weight (12%), adiposity, plasma lipids and induced glucose intolerance (HC vs CC; P<0.05). These were exaggerated by postweaning HFD (HH vs HC; P<0.01), showed doubled energy intake, a 37% increase in body weight, insulin resistance and glucose intolerance (HH vs HC; P<0.01). Exercise reduced fat mass, plasma lipids, HOMA and fasting glucose in HC(EX) (vs HC; P<0.05) and HH(EX) (vs HH; P<0.01). Values in HC(EX) were indistinguishable from CC, however in HH(EX) these metabolic parameters remained higher than the sedentary HC and CC rats (P<0.01). mRNA expression of hypothalamic pro-opiomelanocortin, and adipose tumour necrosis factor α and 11ß-hydroxysteroid dehydrogenase type 1 were reduced by exercise in HH(EX) (vs HH; P<0.05). CONCLUSION: While voluntary exercise almost completely reversed the metabolic effects of maternal obesity in chow fed offspring, it did not fully attenuate the increased adiposity, glucose intolerance and insulin resistance in offspring weaned onto HFD.
Subject(s)
Homeostasis/physiology , Maternal Nutritional Physiological Phenomena , Obesity/metabolism , Physical Conditioning, Animal/physiology , Weaning , 11-beta-Hydroxysteroid Dehydrogenase Type 1/blood , Adiposity , Animal Nutritional Physiological Phenomena , Animals , Appetite/physiology , Blood Glucose/analysis , Blood Pressure , Body Weight , Diet, High-Fat , Dyslipidemias/metabolism , Energy Intake , Fatty Acids, Nonesterified/blood , Female , Hypothalamus/metabolism , Insulin/blood , Insulin Resistance , Leptin/blood , Pro-Opiomelanocortin/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Triglycerides/blood , Tumor Necrosis Factor-alpha/bloodABSTRACT
Maternal obesity has long-term consequences for the development of hypothalamic neurones involved in energy homeostasis and the metabolic profile in offspring. In the present study, we compared the effects of maternal obesity induced by longstanding high-fat diet (HFD) with milder postnatal overfeeding during suckling induced by litter size reduction. Female Sprague-Dawley rats consumed chow (C) or HFD. On postnatal day 1, litters from chow dams were adjusted to three per dam (small litter, CS) versus 12 control (normal litter, CN). Litters from HFD dams were adjusted to 12 per dam and fed HFD after weaning to induce obesity (HN). Thus, two degrees of maternal overnutrition were produced (CS and HN). To test whether postweaning diet can amplify the effects of maternal obesity, male offspring weaned onto chow or HFD were followed to 21 weeks. Maternal postnatal overnutrition (CS) and HFD-induced maternal obesity (HN) increased body weight and fat mass in offspring compared to those from control dams (CN). Significant glucose intolerance was induced by both degrees of maternal overnutrition, but only in offspring consuming HFD. HFD-induced maternal obesity (HN) was linked to increased offspring leptin, insulin, lipids, insulin resistance and hyperphagia, and was exaggerated by postweaning HFD. No effect of maternal postnatal overnutrition (CS) was seen on these parameters. Hypothalamic signal transducer and activator of transcription-3 and suppressor of cytokine signalling-3 mRNA were significantly elevated by maternal HFD (HN) in the HFD-fed offspring. The data obtained suggest that even mild maternal overnutrition (CS) led to increased adiposity, glucose intolerance and altered brain appetite regulators in offspring. A greater impact of HFD-induced maternal obesity was evident. Marked additive effects were observed when animals consumed a HFD postweaning.
Subject(s)
Adiposity/physiology , Appetite/physiology , Biomarkers/metabolism , Brain/metabolism , Maternal Nutritional Physiological Phenomena , Overnutrition/metabolism , Weaning , Adult , Animals , Animals, Newborn/metabolism , Body Weight , Child , Diet , Eating , Female , Glucose/metabolism , Glucose Tolerance Test , Humans , Male , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
Se analizó la actividad en el sistema nervioso central de los extractos acuosos de cuarenta plantas medicinales de Bangladesh mediante el estudio de la duración del sueño inducido por pentobarbital. Doce de las plantas mostraron un aumento significativo de la duración del sueño, mientras que seis mostraron una disminución significativa. Woodfordia fruticosa y Uraria lagopodioides presentaron un mayor efecto depresor que el diazepam
Aqueous extracts of forty medicinal plants of Bangladesh have been screened for central nervous system activity by pentobarbital-induced sleeping time test. While twelve plants showed signifi cant increase in sleeping time, six plants showed significant decrease. Woodfordia fruticosa and Uraria lagopodioides exhibited a better depressant effect than diazepam
