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Genetic expression of microsomal electron transport in mice. Different patterns of dependence of constitutive cytochrome P-450 reductase activity of pyridine nucleotide concentrations.

Cytochrome P-450 reductase and aryl hydrocarbon hydroxylase activities were investigated in hepatic microsomes from untreated C57BL/6J, DBA/2J, B6D2F1, and (B6D2) D2 mice. The dependence of the rate of P-450 reduction on the concentration of added pyridine nucleotide (NADPH or NADH) was biphasic in DBA/2J microsomes but monophasic in C57BL/6J microsomes. Analogous strain-specific patterns were observed when the dependence of the rate of benzpyrene hydroxylation on NADPH concentration was examined. In crosses between the two inbred strains and between B6D2F1 mice and DBA/2J mice, the biphasic pattern for both the reductase and the hydroxylase activities was found to co-segregate with the recessive allele for aromatic hydrocarbon responsiveness. These results might reflect an architectural difference between the microsomal electron transport systems of responsive and nonresponsive mice.

Animals↗

[Genetic expression and morphogenesis of the skin in vertebrates].

Retinoic acid is an exception amongst teratogenic agents: indeed, it not only interferes with morphogenesis, but it also alters positional values, which leads to the formation of additional structures. The latter effect, similar to that of homeotic mutations, which have been characterized in drosophila, is the most instructive way to study morphogenetic processes. Intramniotic injection of retinoic acid into 10-day-old chick embryos causes feather formation on the scales of the anterior side of tarsometatarsus. Likewise, when the upper-lip skin of 13.5-day mouse embryos is treated in vitro with retinoic acid, there is a development of mouse vibrissa hair buds into glands. The expression of retinoic acid nuclear receptors (RARs) has been studied by in situ hybridization during normal morphogenesis of hair vibrissa follicles as well as during retinoic acid-induced glandular metaplasia. During the normal development of hair follicle, only RAR alpha and RAR gamma genes are transcribed, whereas RAR beta gene expression remains undetected by the techniques used. Retinoic acid skin treatment brings about RAR beta expression in the dermis, leading to the formation of glomerular glands. Now, hair, gland, scale or feather differentiation implies dermal-epidermal interactions which have been extensively studied. However, little is known about the language of communication used by the two tissues. Even if the inductive role of the dermis seems dominant, the competence of the epidermis must not be neglected: the latter determines in some cases the type of cutaneous appendage which is formed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes in the genetic expression of membrane proteins as a determinant of myocardial dysfunction.

In most of the cases, cardiac hypertrophy is the physiological adaptation of the heart to a disease, and the causal disease is usually arterial and cardiac failure indicates the limits of the mechanical adaptation. Such an adaptational process is aggravated by an additional factor, namely fibrosis which is not related to mechanical overload, but depends upon ischemia, senescence and hormones or peptides. Myocardial adaptation or dysadaptation is a species-specific process because the regulation of calcium movements, the main myocardial intracellular messenger differs from one animal species to the other. In this chapter, we will use, as a model, the rat, and finally will report what we know concerning the biology of the human failing heart.

Adaptation, Physiological↗

[Multiple genetic expression abnormalities in gastric cancer].

UNLABELLED: By means of LSAB and ABC techniques, the expressions of p53, c-erbB-2, EGFR and ras were examined on 75 cases of gastric cancer (GC) specimens. RESULTS: (1) The positive rate of p53, c-erbB-2, EGFR and ras expression was 41.3%, 18.7%, 61.3% and 46.7%, respectively. The early cases and the intestinal type cases of GC had higher p53 positive rates than those of the advanced and the diffuse type ones, respectively. Two of 4 cases of severe dysplasia lesions adjacent to carcinoma sites were positive. c-erbB-2 positive immunoreactivity was only localized in the cancer cells, and tissues adjacent to the carcinoma sites were negative. Higher frequencies of c-erbB-2 expression were found in the well-differentiated GC. Positive correlation was found between EGFR expression and degree of malignancy of GC. (2) No correlation was found between the expression of c-erbB-2 and EGFR. (3) The expression of ras correlated positively with EGFR expression, but negatively with c-erbB-2 (P < 0.05). (4) No correlation was found between the expression of p53 and other genes examined. The results demonstrate that many gene abnormalities are present in the process of gastrocarcinogenesis.

Female↗

[Genetic expression of nerve growth factor in the central nervous system. Evaluation of an experimental model for Alzheimer's dementia].

INTRODUCTION AND OBJECTIVE: Several authors have suggested that loss of neuronal trophic support may be an important element in the physiopathology of degenerative conditions of the central nervous system such as Alzheimer's dementia, Parkinson's disease or amyotrophic lateral sclerosis amongst others. In the light of present knowledge, the survival of cholinergic populations of the anterior basal cerebrum, closely involved with cognitive processes of memory and learning, is associated with adequate function of the neural growth factor (NGF). These populations are markedly damaged in Alzheimer's disease, and this has been correlated with the progressive loss of memory and intellectual involvement seen in this disorder. The model used in this study was based on section of the septohippocampal connecting pathways, so that transport of regulatory impulses from the hippocampus to the medial septum was interrupted. This has lethal results for the cholinergic neurons of the latter. We have developed a study designed to characterize the expression of the gene of NGF in different regions of the brain, involved in cholinergic neurotransmission in healthy and in damaged tissue. MATERIAL AND METHODS: We used a molecular hybridization technique with a cDNA catheter complementary to the radio-isotope marked NGF human gene. RESULTS AND CONCLUSIONS: The highest levels of expression were found in the healthy cortex and hippocampus. The reduction in the levels of mRNA of NGF in the damaged hippocampus supports the current thesis which considers synaptic activity to be a major regulator of the synthesis of this molecule in the brain.

Alzheimer Disease↗

[Effect of thyroid hormones on the modulation of genetic expression of liver cytosolic malic enzyme, in rats poisoned with hexachlorobenzene].

Hexachlorobenzene (HCB) is a widespread environmental pollutant. Chronic exposure of laboratory animals to HCB triggers porphyria, induction of liver microsomal enzymes, low levels of T4 reproductive dysfunction's, liver and thyroid tumors. Previous findings from our laboratory have shown that HCB increased the activity of the liver thyroid-responsive enzymes: malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) without any change in the mytochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD). In this study we have demonstrated that HCB treatment increased ME mRNA. We also have investigated if HCB affected: a) the thyroid hormone receptor (TR) concentration and binding affinity for its ligands, b) specifically the ME gene expression, or other thyroid hormone responsive enzymes were affected as well, c) Protein/DNA complex formed on the thyroid responsive element (TRE). Livers from female Wistar rats intoxicated with HCB (100 mg/100 g b.w.), for 9 and 15 days, were analyzed. Northern blot hybridization analysis, have demonstrated that ME mRNA levels increased 4 times and 2 times after 9 and 15 days intoxication respectively, without any alterations in the mRNA levels of other thyroid hormone responsive enzymes such as glyceraldheyde 3- phosphate dehydrogenase, phosphoenolpyruvatecarboxikinase and alpha-GPD. These results suggest that HCB affects specifically, ME gene expression. Hepatic T3 and T4 levels evaluated by RIA were not affected by HCB. Scatchard analyses showed that TR affinity and number of sites were not altered after 9 and 15 days of HCB treatment (control, Ka: 1.9 nM, Bmax 3.9 f/mol 100 micrograms DNA: HCD 9 days Ka: 2.1 nM, Bmax 4.5 fmol/100 micrograms DNA: HCB 15 days Ka 1.9 nM. Bmax 5.1 fmol/100 micrograms DNA intoxication, neither at 9 nor at 15 days. Electrophoresis mobility shift assay showed that HCB did not modify nuclear protein extract affinity for the TREs sequence. Our results suggest that TR itself was not directly involved in the induction of ME gene expression by HCB. Nevertheless TR could interact with other transcription factors in the overexpression of ME gene.

Animals↗

Analysis of gene expression in genetic epilepsy-prone rat using a cDNA expression array.

UNLABELLED: Our aim is to search the differential expression genes of genetic epilepsy and establish the groundwork of exploring the pathogenesis of epilepsy on the gene level by using cDNA array technology. METHODS: Gene expression profiles of the cerebral cortex of genetic epilepsy-prone P77PMC rats and normal Wistar rats were established using the Atlas Rat cDNA Expression Array. The difference between gene expression profiles was analyzed using an image analysis instrument. RESULTS: Fifteen genes exhibited a differential expression pattern between the P77PMC rats' and Wistar rats' cerebral cortex, while there maybe many other differential expression genes undiscovered due to having no image analysis software. Among them, the levels of expression of 13 genes were elevated in P77PMC rats as compared to their levels in Wistar rats, in contrast, the levels of expression of two genes were decreased in P77PMC rats. CONCLUSION: There were several differential expression genes between P77PMC rats and Wistar rats. All these genes could play important roles in the pathogenesis of epilepsy.

Animals↗