Induction of apoptosis in starfish eggs requires spontaneous inactivation of MAPK (extracellular signal-regulated kinase) followed by activation of p38MAPK

Mitogen-activated protein kinase (MAPK) (extracellular signal-regulated kinase) prevents DNA replication and parthenogenesis in maturing oocytes. After the meiotic cell cycle in starfish eggs, MAPK activity is maintained until fertilization. When eggs are fertilized, inactivation of MAPK occurs, allowing development to proceed. Without fertilization, highly synchronous apoptosis of starfish eggs starts 10 h after germinal vesicle breakdown, which varies according to season and individual animals. For induction of the apoptosis, MAPK should be activated for a definite period, called the MAPK-dependent period, during which eggs develop competence to die, although the exact duration of the period was unclear. In this study, we show that the duration of the MAPK-dependent period was approximately 8 h. Membrane blebbing occurred approximately 2 h after the MAPK-dependent period. Surprisingly, when MAPK was inhibited by U0126 after the MAPK-dependent period, activation of caspase-3 occurred earlier than in the control eggs. Thus, inactivation of MAPK is a prerequisite for apoptosis. Also, even in the absence of the inhibitor, MAPK was inactivated spontaneously when eggs began to bleb, indicating that inactivation of MAPK after the MAPK-dependent period acts upstream of caspase-3. Inactivation of MAPK also resulted in the activation of p38MAPK, which may contribute to apoptotic body formation.     

Enhancement of antioxidant activity of p-alkylaminophenols by alkyl chain elongation

The initial finding that the p-methylaminophenol (6) exhibited antioxidant activity led us to investigate whether the length of alkyl chains linked to the aminophenol residue might affect antioxidative activity. Therefore, we synthesized p-butylaminophenol (5), p-hexylaminophenol (4), p-octylaminophenol (3), and p-methoxybenzylaminophenol (7). All p-alkylaminophenols quenched alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radicals, with 7 being the most potent DPPH radical scavenger. Lipid peroxidation by rat liver microsomes was reduced by p-alkylaminophenols in dose- and aminophenol alkyl chain length-dependent fashion (3>4>5>6), with 3 being the most potent lipid peroxidation inhibitor, at approximately 350-fold higher potency than 6. These results indicate that elongation of alkyl chains in p-alkylaminophenols may increase antioxidative activity, and that p-alkylaminophenols may potentially be useful in the development of antioxidants.     

Courtship song recognition in the Drosophila melanogaster complex: heterospecific songs make females receptive in D. melanogaster, but not in D. sechellia

Abstract. The courtship song emitted by male wing vibration has been regarded as one of the most important signals in sexual isolation in the species of the Drosophila melanogaster complex. Inter- and intraspecific crosses were observed using males whose wings were removed (mute) or females whose aristae were removed (deaf). Females of D. melanogaster, D. simulans , and D. mauritiana mated with heterospecific males in the song-present condition (cross between normal females and winged males) more often than in the no-song condition (cross between normal females and wingless males or between aristaless females and winged males) or they showed no preference between the two conditions. It is possible that in these females heterospecific courtship songs play a role as if they were conspecific. In contrast, the females of D. sechellia mated with D. melanogaster or D. simulans males in the no-song condition more often than in the song-present condition, suggesting that they reject males with heterospecific song. Female mate recognition depending on the courtship song in D. melanogaster, D. simulans , and D. mauritiana is considered to be relatively broader and that in D. sechellia narrower.     

Switch of histamine receptor expression from H2 to H1 during differentiation of monocytes into macrophages

It is known that histamine suppresses gene expression and synthesis of tumor necrosis factor alpha (TNF-alpha) induced by lipopolysaccharide (LPS) in human peripheral blood mononuclear monocytes (HPM) or alveolar macrophages via histamine H2 receptors. We investigated the effect of histamine and differentiation in macrophages on the expression and secretion of TNF-alpha, TNF-alpha-converting enzyme (TACE), and histamine H1 and H2 receptors by use of a leukemia cell line, U937, and HPM. Differentiation of U937 and HPM cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) enhanced the H1 receptor expression and rather suppressed the H2 receptor, resulting in up-regulation of the histamine-induced expression and secretion of TNF-alpha, modulated via TACE. Therefore, histamine failed to inhibit up-regulated expression of TNF-alpha induced by LPS in macrophages. The switch from H2 to H1 receptors during differentiation in the monocyte/macrophage lineage could participate in the pathogenic processes of atherosclerosis and inflammatory reactions in the arterial wall.     

Induction of tryptophan 2,3-dioxygenase in the mouse endometrium during implantation

Indoleamine 2,3-dioxygenase (IDO) is expressed in trophoblasts and defends the conceptus against rejection by reducing the tryptophan level and suppressing the T cell activity. We isolated a cDNA for tryptophan 2,3-dioxygenase (TDO), another key catabolizing enzyme of tryptophan, from a mouse uterus cDNA library enriched with pregnancy-induced genes. Northern blot and in situ hybridization analyses demonstrated that the TDO mRNA was induced in the decidualized stromal cells around the implanted embryo at the time of implantation. The expression was then upregulated and primarily localized at the mesometrial decidua. TDO mRNA was induced by deciduoma formation as well as embryo transfer but not by ovarian steroid hormones. These findings demonstrated that TDO is induced in the endometrial stromal cells concomitant with decidualization and suggested its involvement in the implantation process by regulating the tryptophan level at the implantation site.     

Glycosylated human interleukin-1α, neoglyco IL-1α, coupled with N-acetylneuraminic acid exhibits selective activities in vivo and altered tissue distribution

In order to study the effect of glycosylation on its biological activities and to develop IL-1 with less deleterious effects, N-acetylneuraminic acid (NeuAc) with C9 spacer was chemically coupled to human recombinant IL-1. NeuAc-coupled IL-1 (NeuAc-IL-1) exhibited reduced activities in vitro and receptor-binding affinities by about ten times compared to IL-1. In this study, we examined a variety of IL-1 activities in vivo. NeuAc-IL-1 exhibited a marked reduction in the activity to up-regulate serum IL-6, moderate reduction in the activities to up-regulate serum amyloid A and NOx. However, it exhibited comparable activities as IL-1 to down-regulate serum glucose and to improve the recovery of peripheral white blood cells from myelosuppression in 5-fluorouracil-treated mice. In addition, tissue level of NeuAc-IL-1 was high compared to IL-1. These results indicate that coupling with NeuAc enabled us to develop neo-IL-1 with selective activities in vivo and enhanced tissue level.