Biological signals最新文献

Expression of thymidine kinase gene in normal human diploid cells is both cell cycle- and age-dependent and appears to be transcriptionally regulated. Strong DNA protein binding with a 28-bp fragment (-91/-64) that contains the distal inverted CCAAT box is observed in serum-stimulated young (low population doubling level) IMR-90 cells but not in senescent cells. This cell cycle- and age-dependent binding factor was termed CBP/ tk, indicating CCAAT binding protein for the thymidine kinase gene. Based on immunoshift assay and purification, it has been suggested that CBP/tk is equivalent to NF-Y, previously identified as the binding protein for the Y box within E alpha gene promoter. In this study, we examined the mRNA level and protein amount of NF-Y, proteins in young and old IMR-90 cells during serum stimulation by Northern and Western blot blot analyses. In addition, we compared (1) the turnover rate of NF-Y in IMR-90 cells with that of CBP/tk binding activity and (2) the levels of NF-Y and CBP/tk in normal and cancer cells. Both NF-YA and NF-YB were constitutively expressed at mRNA level in IMR-90 cells. However, expression of NF-YA, and to a lesser degree, NF-YB, at the protein level were clearly age-dependent. The half-life of NF-YA and NF-YB were, respectively, 4- and > 10-fold longer than that of CBP/tk binding activity in IMR-90 cells. In addition, we found that the amount of NF-Y did not correlate with the overexpression of CBP/tk binding activity in HeLa cells. Taken together, our results suggested that although CBP/tk may contain NF-YA or related proteins, NF-A and NF-YB alone may not account for all the characteristics of CBP/tk observed in normal and transformed human cells.

A characteristic feature of aging is a progressive impairment in the ability to adapt to environmental challenges. The purpose of this article is to review the evidence of an attenuated response to heat and physiological stresses in a number of mammalian aging model systems, including the human diploid fibroblasts in culture, whole animals and animal-derived cells and cell cultures, as well as peripheral blood mononuclear cells obtained from human donors. Analyses of the regulation and function of heat shock factor 1 (HSF1), a transcription factor that mediates the response to heat shock, showed that while the relative abundance of both the hsf1 transcript and the HSF1 protein did not change as a function of age, the responsiveness of HSF1 to heat-induced activation, as measured by its trimerization and ability to bind to the heat shock element consensus sequence, was inversely related to the age of the cells used. Given the fundamentally important role of heat shock proteins (HSPs) in many aspects of protein homeostasis and signal transduction it seems likely that the inability, or compromised ability, of aging cells and organisms to activate HSF1 and produce HSPs in response to stress would contribute to the well-known increase in morbidity and mortality of the aged when challenged.

Cyclic ADP-ribose is a cyclic nucleotide with Ca2+ signaling functions. It was first discovered in sea urchin eggs and has since been shown to be active in a variety of cells. Another Ca2+ release mechanism recently described in the eggs is mediated by nicotinic acid dinucleotide phosphate, a derivative of NADP+. This article summarizes current results on these two novel Ca(2+)-mobilizing pathways that are independent of inositol trisphosphate.

In goldfish, maturational gonadotropin (GTH) and growth hormone (GH) release are stimulated by two native GTH-releasing hormones (sGnRH and cGnRH-II). Both GnRHs stimulate GTH and GH release via activation of phospholipase C, protein kinase C, Ca2+ entry through voltage-sensitive channels and calmodulin. However, sGnRH-induced GTH release also involves arachidonic acid and intracellular Ca2+ components absent from its action on GH, as well as from cGnRH-II action on GTH and GH secretion. The relative roles and interactions of these signaling pathways in mediating sGnRH and cGnRH-II action on acute and prolonged GTH and GH release are compared. How two GnRHs bind to similar receptors but induce similar and dissimilar transduction mechanisms in two cell types and within one cell type is unknown.

In mammals, the uterus is modified to be able to contain a pregnancy and nurture the developing embryo. In deciduate mammals, this is apparently due to formation of a special compartment, lined with decidual tissue, in which a semi-allogeneic (or even allogeneic, after embryo transplantation) pregnancy is accommodated. This review treats the mechanisms which have been evoked to explain the implantation of the egg and the decidualization of the implanting endometrium. At least three different neurochemicals have been considered to mediate induction of this response: histamine, prostaglandins and platelet-aggregating factor. Their importance is reviewed. The ability of the endometrium to transform into decidual tissue is contingent on the presence of the epithelium. The role of the epithelium is temporary, however, since it dies and is sloughed within a day of the induction. Studies of progesterone-dependent changes in the epithelial reaction to preimplantation pregnancy are considered.

The ovarian response to the stimulatory actions of pituitary gonadotropins is modulated by the local production and action of local factors. Current advances in biochemical and molecular research techniques have facilitated the progress in our understanding of how prostaglandins (PGs) are inherently involved in the physiological events influencing ovarian cellular function in all mammalian species, particularly during ovulation and luteolysis. The purpose of this review is to incorporate recent findings with previous data, highlighting the novel characterization of the PG F2 alpha receptor and other PG receptors, and their intracellular signaling mechanisms in relation to ovarian function.

Gonadotropin-releasing hormone (GnRH) plays a major role in the endocrine control of reproduction. GnRH, released from the hypothalamus, acts upon the pituitary to stimulate LH and FSH secretion. In addition, GnRH also functions as a local regulator in a number of tissues and cell lines. GnRH interacts with a membrane receptor which belongs to the G-protein-coupled receptor family. The GnRH-R is encoded by a single-copy gene consisting of three exons and two introns. Consistent with the sites of its action, GnRH-R mRNA has been found in the brain, pituitary, gonads, placenta, as well as a number of carcinoma tissues and cells. GnRH-R mRNA level in the pituitary and gonads is controlled by a number of physiological regulators, such as GnRH, gonadotropin, estradiol and progesterone.

There is increasing evidence that activin may act as an autocrine/paracrine regulator of ovarian functions. Activin subunit mRNAs as well as activin immunoreactivities have been detected in the human ovary. Activin alters granulosa cell proliferation and steroidogenesis. The effect of activin is most likely mediated through specific receptors as mRNAs encoding several forms of activin receptors, namely ActR-I, ActR-IB, ActR-II and ActR-IIB are found in the preovulatory follicles as well as in cultured granulosa-luteal cells. Activin-binding protein, follistatin (FS), is also produced in the human ovary. In addition to neutralizing the effect of activin on steroid production, FS on its own also enhances estradiol production, an effect similar to that seen after activin treatment. These findings strongly suggest that activin and FS are important local regulators of steroidogenesis in the human ovary.

Extracellularly applied ATP, UTP and UDP induce a transient increase in the intracellular Ca2+ concentration of mammary cells via a P2U receptor. The P2U receptor in the mammary tumor cell line MMT060562 was cloned and expressed in the human leukemia cell line K-562. The deduced amino acid sequence of the mammary tumor cell P2U receptor was 98% homologous with that of mouse NG108-15 cells. It was a member of the superfamily of GTP-binding-protein-coupled receptors. ATP and UTP induced the increase in the intracellular concentrations of Ca2+ and inositol-1,4,5-trisphosphate in both mammary tumor cells and P2U-receptor-expressed K562 cells. Dose-response curves on the production of inositol-1,4,5-trisphosphate and Ca2+ by ATP and UTP were consistently similar. Injection of GTP enhanced the ATP-induced outward current and injection of GTP gamma S induced a repetitive outward current. Both pertussis and cholera toxins did not affect ATP-induced calcium increase. It was suggested that the P2U receptor coupled with pertussis- and cholera-toxin-insensitive GTP-binding proteins and activated phosphoinositide turnover.

Angiotensin II (Ang II) is an important stress hormone. Circulating and tissue Ang II are significantly increased in both acutely and chronically stressed animals. In humans, the plasma Ang II content increases markedly after sprinting, as does cortisol. The present paper reviews recent studies with special reference to the correlation between the renin-angiotensin system (RAS) and the hypothalamus-pituitary-adrenal cortex system and sympathetic-adrenal medulla system during stress. We would like to suggest that in the stress response, Ang II is not only a stress hormone to various peripheral organs, but is also a notable factor in initiating the systemic stress response from central to peripheral tissues. The RAS is therefore a stress hormone response system similar to the hypothalamus-pituitary-adrenal cortex system and the sympathetic-adrenal medulla system.