Mechanism of hyperproteinemia-induced blood cell homeostasis imbalance in an animal model

Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration (PPC). It is often clinically complicated by malignant diseases or severe infections. Research on the molecular mechanism of High PPC (HPPC) is scant. Here, an animal model of primary hyperproteinemia was constructed in an invertebrate, Bombyx mori, to investigate the effect of HPPC on circulating blood cells. We showed that HPPC affected blood cell homeostasis and enhanced blood cell phagocytosis, leading to increased reactive oxygen species levels, and induced programmed cell death that depended on the endoplasmic reticulum-calcium ion signaling pathway. HPPC induced the proliferation of blood cells, mainly granulocytes, by activating the JAK/STAT signaling pathway. Supplementation with endocrine hormone active substance 20E significantly reduced the impact of HPPC on blood cell homeostasis. Herein, we reported a novel signaling pathway by which HPPC affected blood cell homeostasis, which was different from hyperglycemia, hyperlipidemia, and hypercholesterolemia. In addition, we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early monitoring index for hyperproteinemia.

Molecular changes associated with migratory departure from wintering areas in obligate songbird migrants

Daylength regulates the development of spring migratory and subsequent reproductive phenotypes in avian migrants. This study used molecular approaches, and compared mRNA and proteome-wide expressions in captive redheaded buntings that were photostimulated under long days (LD) for 4 days (early stimulated, LD-eS) or for ∼3 weeks until each bird had shown successive 4 nights of Zugunruhe (stimulated, LD-S); controls were maintained under short-days. After ∼3 weeks of LD, photostimulated indices of the migratory preparedness (fattening, weight gain and Zugunruhe) were paralleled with upregulated expression of acc, dgat2 and apoa1 genes in the liver, and of cd36, fabp3 and cpt1 genes in the flight muscle, suggesting an enhanced fatty acids (FAs) synthesis and transport in the LD-S state. Concurrently elevated expression of genes involved in the calcium-ion signaling and transport (camk1 and atp2a2; camk2a in LD-eS instead), cellular stress (hspa8 and sod1, not nos2) and metabolic pathways (apoa1 and sirt1), but not of the genes associated with migratory behaviour (adcyap1 and vps13a), were found in the mediobasal hypothalamus (MBH). Further, the MBH-specific quantitative proteomics revealed that out of 503 annotated proteins, 28 were differentially expressed (LD-eS vs. LD-S: 21 up- and 7 down-regulated) and they enriched five physiological pathways that are associated with fatty acids transport and metabolism. These first comprehensive results on gene and protein expressions suggest that changes in molecular correlates of fatty acids transport and metabolism may aid the decision for migratory departure from wintering areas in obligate songbird migrants.

Influence of antifertility agents Dutasteride and Nifedipine on CatSper gene level in epididymis during sperm maturation in BALB/c mice

Calcium (Ca2+) signaling is critical for successful fertilization. In spermatozoa, capacitation, hyperactivation of motility and the acrosome reaction are all mediated by increases in intracellular Ca2+ through CatSper (sperm-specific cation channel). The CatSper channel complex contains four pore-forming α subunits (CatSper1–4) and five accessory subunits called β, δ, ε, γ and ζ. Genetic deletion of any of the four CatSper genes in mice results in loss of hyperactivated motility and male infertility. Despite their vital role in male fertility, almost very little is known about influence of antifertility agents on CatSper gene expression in epididymis and epididymal spermatozoa. Therefore, we performed quantitative real-time qPCR analysis for CatSper expression in the epididymis and epididymal sperm of BALB/c mice after treatment with Dutasteride (DS), a dual 5-α reductase inhibitor and Nifedipine (NF) a calcium channel blocker as positive control. We observed that treatment with antifertility agents Dutasteride and Nifedipine induced significant decreases in the caput and cauda epididymal sperm counts, motility and fertility which could partly be attributed to alteration in the normal morphology of the sperm associated with downregulation/upregulation of CatSper mRNAs in epididymis and epididymal spermatozoa of male BALB/c mice. These can be explained on the basis of interference with mechanisms affecting calcium ion signaling resulting in changes in intracellular calcium required for sperm activity, finally affecting sperm maturation and fertility of male BALB/c mice. These studies provide some novel avenues for developing new male contraceptives in future.

Serial Dissection of Parasite Gene Families

Calcium ion signaling regulates central aspects of the biology controlling stage and life cycle transitions of apicomplexan parasites. In the current issue ofInfection and Immunity, Long and coworkers (S. Long, Q. Wang, and L. D. Sibley, Infect Immun 84:1262–1273, 2016,http://dx.doi.org/10.1128/IAI.01173-15) describe a powerful genetic system enabling reliable serial genetic dissection of a large gene family encoding novel calcium-dependent protein kinases (CDPKs) that provides new insights into the roles of CDPKs duringToxoplasma gondiiinfection.

Actin foci facilitate activation of the phospholipase C-γ in primary T lymphocytes via the WASP pathway

Wiscott Aldrich Syndrome protein (WASP) deficiency results in defects in calcium ion signaling, cytoskeletal regulation, gene transcription and overall T cell activation. The activation of WASP constitutes a key pathway for actin filament nucleation. Yet, when WASP function is eliminated there is negligible effect on actin polymerization at the immunological synapse, leading to gaps in our understanding of the events connecting WASP and calcium ion signaling. Here, we identify a fraction of total synaptic F-actin selectively generated by WASP in the form of distinct F-actin ‘foci’. These foci are polymerized de novo as a result of the T cell receptor (TCR) proximal tyrosine kinase cascade, and facilitate distal signaling events including PLCγ1 activation and subsequent cytoplasmic calcium ion elevation. We conclude that WASP generates a dynamic F-actin architecture in the context of the immunological synapse, which then amplifies the downstream signals required for an optimal immune response.