Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Yucheng (oil disease) is a clinical and metabolic syndrome reported in Taiwanese who consumed rice oil contaminated with large amounts of various polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs), including the 2,3,4,7,8- and 1,2,3,4,7,8-PCDF congeners which are similar in structure and toxicity to 2,3,7,8-tetrachlorodibenzo-p-dioxin. A well known characteristic of Yucheng is the marked decrease in birth weights, although the underlying mechanism of this effect is unclear. Placental epidermal growth factor (EGF) receptor binding and autophosphorylation studies were done using tissue samples taken from Yucheng and unexposed control patients. EGF-stimulated receptor autophosphorylation of the human placental EGF receptor in the Yucheng subjects was decreased more than 60% of control levels, 4-5 years after the exposure had occurred. The decrease in EGF receptor phosphorylation was significantly correlated with decrease in birth weights. Nonlinear regression analysis of the 125I-EGF receptor binding data revealed that there were two distinct EGF receptor binding isotherms representing the high affinity-low capacity (HALC) and the low affinity-high capacity (LAHC) binding sites. In contrast to the placental EGF-stimulated phosphorylation data described above, the binding kinetics of the EGF receptor were not significantly altered in the control [HALC site Kd = 0.10 +/- 0.02 (SE) nM, Bmax = 788 +/- 255 fmol/mg of protein; LAHC site Kd = 17.4 +/- 8.2 nM, Bmax = 62 +/- 32 pmol/mg) compared to the Yucheng subjects (HALC site Kd = 0.11 +/- 0.02 nM, Bmax = 784 +/- 305 fmol/mg; LAHC site Kd = 49.5 +/- 24.7 nM, Bmax = 147 +/- 80 pmol/mg). GC-MS analysis of placental specimens showed elevated levels of selected PCB and PCDF congeners in the Yucheng compared to control individuals. Total PCB levels were 0.5 +/- 0.2 ppb and 20.0 +/- 4.8 ppb for the control and Yucheng subjects, respectively. A significant dose-response relationship was observed between the placental EGF receptor phosphorylation levels and the PCB concentrations (total or concentrations of 2,2',4,4',5,5'-hexa- and 2,2'3,3'4,4',5-heptachlorobiphenyls). In contrast, no significant relationship was found between the EGF receptor phosphorylation activity and the 2,3,4,7,8- or 1,2,3,4,7,8-PCDF congeners, which were at nondetectable levels in the control and between 104 and 374 parts per trillion in the Yucheng subjects. In summary, our data reveal that decreased placental EGF receptor phosphorylation capacity is associated with decreased birth weight. Furthermore, PCB tissue concentrations might be a better predictor of effects than are PCDF concentrations.
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PMID:Decreased human birth weights after in utero exposure to PCBs and PCDFs are associated with decreased placental EGF-stimulated receptor autophosphorylation capacity. 311 85

A number of lines of evidence, including nonhuman primate and human studies, suggest that regulatory pathways similar to those invoked by caloric restriction (CR) may be involved in determining human longevity. Thus, pharmaceuticals capable of mimicking the molecular mechanisms of life- and health-span extension by CR (CR mimetics) may have application to human health. CR acts rapidly, even in late adulthood, to begin to extend life- and health-span in mice. We have linked these effects with rapid changes in the levels of specific gene transcripts in the liver and the heart. Our results are consistent with the rapid effects of caloric intake on the lifespan and/or biochemistry and physiology of Drosophila, rodents, rhesus macaques and humans. To test the hypothesis that existing pharmaceuticals can mimic the physiologic effects of CR, we evaluated the effectiveness of glucoregulatory drugs and putative cancer chemo-preventatives in reproducing the hepatic gene-expression profiles produced by long-term CR (LTCR). We found that 8 weeks of metformin treatment was superior to 8 weeks of CR at reproducing the specific changes in transcript levels produced by LTCR. Consistent with these results, metformin reduces cancer incidence in diabetic humans and ameliorates the onset and severity of metabolic syndrome. Metformin extends the mean and maximum lifespans of female transgenic HER-2/neu mice by 8% and 13.1% in comparison with control mice. Phenformin, a close chemical relative of metformin, extends lifespan and reduces tumor incidence in C3H mice. These results indicate that gene-expression biomarkers can be used to identify promising candidate CR mimetics.
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PMID:Use of microarray biomarkers to identify longevity therapeutics. 1644 42

We examined the role of epidermal growth factor (EGF) receptor in the pathogenesis of leptin-induced hypertension in the rat. Leptin, administered in increasing doses (0.1-0.5 mg/kg/day) for 10 days, increased phosphorylation levels of non-receptor tyrosine kinase, c-Src, EGF receptor and extracellular signal-regulated kinases (ERK) in aorta and kidney, which was accompanied by the increase in plasma concentration and urinary excretion of isoprostanes and H2O2. Blood pressure and renal Na+,K+-ATPase activity were higher, whereas urinary sodium excretion was lower in animals receiving leptin. The effects of leptin on renal Na+,K+-ATPase, natriuresis and blood pressure were abolished by NADPH oxidase inhibitor, apocynin, Src kinase inhibitor, PP2, EGF receptor inhibitor, AG1478, protein farnesyltransferase inhibitor, manumycin A, and ERK inhibitor, PD98059. In contrast, inhibitors of insulin-like growth factor-1 and platelet-derived growth factor receptors, AG1024 and AG1295, respectively, only slightly reduced ERK phosphorylation and had no effect on blood pressure in rats receiving leptin. These data indicate that: (1) experimental hyperleptinemia is associated with oxidative stress and c-Src-dependent transactivation of the EGF receptor, which stimulates ERK in vascular wall and the kidney, (2) overactivity of EGF receptor-ERK pathway contributes to leptin-induced hypertension by stimulating renal Na+,K+-ATPase and reducing sodium excretion, (3) inhibitors of c-Src, EGF receptor and ERK may be considered as a novel therapy for hypertension associated with hyperleptinemia, e.g. in patients with obesity and metabolic syndrome.
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PMID:Transactivation of epidermal growth factor receptor in vascular and renal systems in rats with experimental hyperleptinemia: role in leptin-induced hypertension. 1828 56

Light-at-night has become an increasing and essential part of the modern lifestyle and leads to a number of health problems, including excessive body mass index, cardiovascular diseases, diabetes, and cancer. The International Agency for Research on Cancer (IARC) Working Group concluded that "shift-work that involves circadian disruption is probably carcinogenic to humans" (Group 2A) [1]. According to the circadian disruption hypothesis, light-at-night might disrupt the endogenous circadian rhythm and specifically suppress nocturnal production of the pineal hormone melatonin and its secretion into the blood. We evaluated the effect of various light/dark regimens on the survival, life span, and spontaneous and chemical carcinogenesis in rodents. Exposure to constant illumination was followed by accelerated aging and enhanced spontaneous tumorigenesis in female CBA and transgenic HER-2/neu mice. In male and female rats maintained at various light/dark regimens (standard 12:12 light/dark [LD], the natural light [NL] of northwestern Russia, constant light [LL], and constant darkness [DD]) from the age of 25 days until natural death, it was found that exposure to NL and LL regimens accelerated age-related switch-off of the estrous function (in females), induced development of metabolic syndrome and spontaneous tumorigenesis, and shortened life span both in male and females rats compared to the standard LD regimen. Melatonin given in nocturnal drinking water prevented the adverse effect of the constant illumination (LL) and natural light (NL) regimens on the homeostasis, life span, and tumor development both in mice and rats. The exposure to the LL regimen accelerated colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH) in rats, whereas the treatment with melatonin alleviated the effects of LL. The maintenance of rats at the DD regimen inhibited DMH-induced carcinogenesis. The LL regimen accelerated, whereas the DD regimen inhibited both mammary carcinogenesis induced by N-nitrosomethylurea and transplacental carcinogenesis induced by N-nitrosoethylurea in rats. Treatment with melatonin prevented premature aging and tumorigenesis in rodents. The data found in the literature and our observations suggest that the use of melatonin would be effective for cancer prevention in humans at risk as a result of light pollution.
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PMID:Light-at-night-induced circadian disruption, cancer and aging. 2323 93