Biomedical subjects

J-M Gasc

Publications and source records attributed to J-M Gasc.

5 recordsLinked to original sources

PubMed2004

Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma.

The expression and function in growth and apoptosis of the renin-angiotensin system (RAS) was evaluated in human glioblastoma. Renin and angiotensinogen (AGT) mRNAs and proteins were found by in situ hybridisation and immunohistochemistry in glioblastoma cells. Angiotensinogen was present in glioblastoma cystic fluids. Thus, human glioblastoma cells produce renin and AGT and secrete AGT. Human glioblastoma and glioblastoma cells expressed renin, AGT, renin receptor, AT(2) and/or AT(1) mRNAs and proteins determined by RT-PCR and/or Western blotting, respectively. The function of the RAS in glioblastoma was studied using human glioblastoma cells in culture. Angiotensinogen, des(Ang I)AGT, tetradecapaptide renin substrate (AGT1-14), Ang I, Ang II or Ang III, added to glioblastoma cells in culture, did not modulate their proliferation, survival or death. Angiotensin-converting enzyme inhibitors did not diminish glioblastoma cell proliferation. However, the addition of selective synthetic renin inhibitors to glioblastoma cells decreased DNA synthesis and viable tumour cell number, and induced apoptosis. This effect was not counterbalanced by concomitant addition of Ang II. In conclusion, the complete RAS is expressed by human glioblastomas and glioblastoma cells in culture. Inhibition of renin in glioblastoma cells may be a potential approach to control glioblastoma cell proliferation and survival, and glioblastoma progression in combination therapy.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2004

Functional characterization of Cx43 based gap junctions during spermatogenesis.

In the testis, spermatogenesis is a highly regulated process that includes germ cell multiplication and differentiation supported by Sertoli cells. Gap junction intercellular communication (GJIC), that is known to play an important role in the control of cell proliferation and differentiation, allows communication between adjacent cells. Gap junctions are present within the seminiferous epithelium but the precise nature of coupled cells is not yet identified. By applying a dye-transfer assay to testis, we demonstrated that coupling was basally located in the tubular compartment between adjacent Sertoli cells, between Sertoli cells and spermatogonia and early and late spermatocytes, but not between Sertoli cells and spermatids. Furthermore, no dye transfer occurred from germ cells to Sertoli cells. Specificity of the gap junction coupling was verified with known gap junction inhibitors such as oleamide, heptanol, and glycyrrhetinic acid. We developed a sophisticated assay that allows correlating the in vivo dye transfer with cell morphological identification and Cx43 expression. This approach demonstrated the Cx43 participation in the coupling. Interestingly Cx43 expression and dye-coupling varied with the stages of spermatogenesis. Our results suggest that Cx43 based gap junctions form a transversal and longitudinal intercellular communication network within seminiferous tubules, and that specific communication territories are formed within the seminiferous tubules to ensure the synchronization of germ cell proliferation and differentiation.

Animals↗

PubMed2003

Maturation-dependent changes of angiotensin receptor expression in fowl.

An angiotensin (ANG) receptor homologous to the type 1 receptor (AT1) has been cloned in chickens (cAT1). We investigated whether cAT1 expression in various tissues shows maturation/age-dependent changes. cAT1 mRNA levels detected in renal glomeruli [in situ hybridization (ISH)] and kidney extract (RT-PCR) are significantly (P < 0.01) higher in 19-day embryos (EB) than in chicks (CH, 2-3 wk) and pullets/cockerels (PL/CK, 14-16 wk). The levels in adrenal glands (concentrated in subcapsular regions) are high in EB and further increased in CH and PL/CK. cAT1 mRNA is also detectable in smooth muscle (SM)/adventitia of EB and CH aorta and in the adventitia, but not SM, from PL/CK aortas. The endothelia from small arteries and arterioles, but not from aorta, express cAT1 mRNA (ISH). In all age groups, ANG II induces profound endothelium-dependent relaxation of abdominal aorta, partly (37-47%) inhibitable (P < 0.01) by Nomega-nitro-l-arginine methyl ester (l-NAME, 10(-4) M), suggesting the presence of ANG receptor in endothelium. l-NAME-resistant ANG II relaxation, examined in a limited number of EB or CH aortas, was reduced by 125 mM K+ or apamin plus charybdotoxin. The results suggest that 1) cAT1 is present in kidney, adrenal gland, and vascular endothelium (heterogeneity exists among arteries) of EB, CH, and PL/CK, and in aortic SM/adventitia of EB/CH but only in adventitia of PL/CK; 2) levels of cAT1 gene expression change during maturation in a tissue-specific manner; and 3) ANG II-induced relaxation may be partly attributable to nitric oxide and potassium channel activation.

Adrenal Glands↗

PubMed2003

Expression of Tie-2 in human peripheral and autonomic nervous system.

Tie-2, a tyrosine kinase receptor, is essential for vascular integrity by regulating cellular adhesion between pericytes and endothelial cells. The aim of this study was to identify sites of expression of Tie-2 other than the vasculature. Tie-2 expression was first detected in human colon by Western blotting and reverse-transcription-polymerase chain reaction (RT-PCR) in tissue extracts. The presence of the Tie-2 mRNA and protein was detected by immunohistochemistry and in situ hybridization in cells of the colon myenteric and submucosal plexus, in both neuronal and Schwann cells. Tie-2 protein was also found in the nervous system of the female urogenital tract. In the human sciatic nerve and schwannoma, RT-PCR, Western blotting and immunohistochemistry analysis further confirmed the presence of Tie-2 mRNA and protein in non-autonomic peripheral nervous tissue. In conclusion, using several approaches and tissues we have demonstrated the presence of Tie-2 in human peripheral and autonomic nervous tissue, suggesting a role for Tie-2 in neural tissue. Thus, attempts to disrupt the tumour vessels by manipulation of the Tie-2 system in tumours may result in side-effects in peripheral nerves.

Colon↗

PubMed2002

Krit1/cerebral cavernous malformation 1 mRNA is preferentially expressed in neurons and epithelial cells in embryo and adult.

Cavernous malformations are capillaro-venous lesions mostly located within the central nervous system (CCM/OMIM#116860) and occasionally within the skin and/or retina. They occur as a sporadic or hereditary condition. Three CCM loci have been mapped, and the sole gene identified so far, CCM1, has been shown to encode KRIT1, a protein of unknown function. In an attempt to get some insight on the relationship between KRIT1 mutations and CCM lesions, we investigated Krit1 mRNA expression during mouse development from E7.5 to E20.5 and in adult tissues, of both mouse and human origin. A ubiquitous Krit1 mRNA expression was detected from E7.5 up to E9.5. Then, it became progressively restricted from E10.5 to E12.5, to become detectable later essentially in the nervous system and various epithelia. Strong labelling was observed in neurons in the brain, cerebellum, spinal cord, retina and dorsal root ganglia. In epithelia, Krit1 mRNA expression was detected in differentiating epidermal, digestive, respiratory, uterine and urinary epithelia. A similar pattern of expression persisted in mouse and man adult nervous system and epithelia. Unexpectedly, in vascular tissues, expression of Krit1 was detected only in large blood vessels of the embryo.

Adult↗