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Biomedical subjects

A Land

Publications and source records attributed to A Land.

8 recordsLinked to original sources
PubMed2003

Activation of multiple signal transduction pathways by glucocorticoids: protection of ovarian follicular cells against apoptosis.

We have recently demonstrated that glucocorticoids protect against serum-deprivation, cAMP-, TNFalpha-, and p53-induced apoptosis in ovarian follicular cells involved in up-regulation of Bcl-2. We demonstrated that dexamethasone, which enhances steroidogenesis by up-regulation of the p450scc enzyme system, stimulates the MAPK cascade by phosphorylation of ERK1, ERK2 as well as by Akt phosphorylation within 1-5min with no effect on p38 MAPK phosphorylation. Moreover, glucocorticoids enhance expression of connexin 43, formation of gap junctions, expression of cadherins, and formation of adherence junctions within 24h of hormone stimulation of ovarian granulosa cells. It is suggested that the protective effects of glucocorticoids against apoptosis are mediated by both genomic and non-genomic mechanisms. Moreover, for the first time we show that protein phosphorylation, cell-cell contact, and intracellular communication are important mediators in glucocorticoid protection against apoptosis in ovarian follicular cells.

Animals↗
PubMed2003

Alternative pathways of ovarian apoptosis: death for life.

Ovarian cell death is an essential process for the homeostasis of ovarian function in human and other mammalian species. It ensures the selection of the dominant follicle and the demise of excess follicles. In turn, this process minimizes the possibility of multiple embryo development during pregnancy and assures the development of few, but healthy embryos. Degeneration of the old corpora lutea in each estrus/menstrual cycle by programmed cell death is essential for maintaining the normal cyclicity of ovarian steroidogenesis. Although there are multiple pathways that can determine cell death or survival, crosstalk among endocrine, paracrine and autocrine factors, as well as among protooncogenes, tumor suppressor genes, survival genes and death genes, play an important role in determining the fate of ovarian somatic and germ cells. The establishment of immortalized rat and human steroidogenic granulosa cell lines and the investigation of pure populations of primary granulosa cells allows for systematic studies of the mechanisms that control steroidogenesis and apoptosis of granulosa cells. We have discovered that during initial stages of granulosa cell apoptosis progesterone production does not decrease. In contrast, we found that it is elevated for up to 24hr following the onset of the apoptotic stimuli exerted by starvation, cAMP, p53 or tumor necrosis factor alpha stimulation, before total cell collapse. These observations raise the possibility for an alternative unique apoptotic pathway, one that does not involve mitochondrial cytochrome C release associated with the destruction of mitochondrial structure and steroidogenic function. Using mRNA from apoptotic cells and Affymetrix DNA microarray we discovered that Granzyme B, a protease that normally resides in T cytotoxic lymphocytes and natural killer cells of the immune system is expressed and activated in granulosa cells, thereby allowing the apoptotic signals to bypass mitochondrial signals for apoptosis, which can preserve their steroidogenic activity until complete cell destruction. This unique apoptotic pathway assures the cyclicity of estradiol and progesterone release in the estrus/menstrus cycle even during the initial stage of apoptosis.

Animals↗
PubMed2001

Folding of the human immunodeficiency virus type 1 envelope glycoprotein in the endoplasmic reticulum.

The lumen of the endoplasmic reticulum (ER) provides a unique folding environment that is distinct from other organelles supporting protein folding. The relatively oxidizing milieu allows the formation of disulfide bonds. N-linked oligosaccharides that are attached during synthesis play multiple roles in the folding process of glycoproteins. They stabilize folded domains and increase protein solubility, which prevents aggregation of folding intermediates. Glycans mediate the interaction of newly synthesized glycoproteins with some resident ER folding factors, such as calnexin and calreticulin. Here we present an overview of the present knowledge on the folding process of the heavily glycosylated human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein in the ER.

Amino Acid Sequence↗
PubMed1999

HIV-1 evolves into a nonsyncytium-inducing virus upon prolonged culture in vitro.

HIV-1 LAI is a syncytium-inducing (SI) virus with a broad host cell range. We previously isolated a LAI variant that improved replication in the SupT1 T cell line due to mutations within the C1 and C4 constant regions of the Env protein. We now report that this variant exhibits a severely restricted host cell range, as replication in other T cell lines and primary cells was abolished. Several Env-mediated functions were analyzed to provide a mechanistic explanation for this selective adaptation. The change in host cell tropism was not caused by a switch to a SupT1-specific coreceptor. Biosynthesis of the variant Env glycoprotein was not improved in SupT1 cells, and in fact a small defect in intracellular Env processing was observed. SupT1 infection assays did not reveal an improved Env function either, and a dramatic loss of infectivity was measured with other cell types. The Env-mutated HIV-1 reached an approximately fivefold higher level of virus production in SupT1 cells at the peak of infection. Unlike the LAI virus, the variant did not trigger the formation of syncytia. Our combined results suggest that the HIV-1 variant allows the infected host cell to survive longer, thus producing more viral progeny. The intricate virus-cell interaction results in a balance between optimal virus replication and host cell survival, causing a cytopathic SI isolate to evolve toward a nonsyncytium-inducing (NSI) phenotype in cell culture. These findings may help explain the absence of SI variants in the initial phase of HIV-1 infection, and the results dispute the notion that HIV-1 evolution should always go from the NSI to SI phenotype.

Adaptation, Physiological↗