Ticks are obligatory blood feeding ectoparasites, which continuously attach to their hosts for 1-2 weeks. There are many biologically active compounds in tick salivary glands interfering host haemostatic system and to successfully obtain blood meal. Several platelet aggregation inhibitors have been identified from ticks. A family of conserved peptides, which were identified from transcriptome analysis of many tick salivary glands, were found to contain unique primary structure including predicted mature peptides of 39-47 amino acid residues in length and a Pro/Glu(P/E)-Pro/His(P/H)-Lys-Gly-Asp(RGD) domain. Given their unique structure and RGD domain, they are considered a novel family of disintegrins that inhibit platelet aggregation. One of them (YY-39) was tested for its effects on platelets and thrombosis in vivo. YY-39 was found effectively to inhibit platelet aggregation induced by adenosine diphosphate (ADP), thrombin and thromboxane A2 (TXA2). Furthermore, YY-39 blocked platelet adhesion to soluble collagen and bound to purified GPIIb/IIIa in a dose-dependent manner. In in vivo experiments, YY-39 reduced thrombus weight effectively in a rat arteriovenous shunt model and inhibited thrombosis in a carrageenan-induced mouse tail thrombosis model. Combined with their prevalence in ticks and platelet inhibitory functions, this family of peptides might be conserved tick anti-haemostatic molecules.
The cause and risk factors of Alzheimer's disease (AD) are largely unknown. Studies on possible radiation-induced AD-like pathogenesis and behavioral consequences are important because humans are exposed to ionizing radiation (IR) from various sources. It was reported that total-body irradiations (TBI) at 10 cGy of low linear energy transfer (LET) X-rays to mice triggered acute transcriptional alterations in genes associated with cognitive dysfunctions. However, it was unknown whether low doses of IR could induce AD-like changes late after exposure. We reported previously that 10 cGy X-rays induced early transcriptional response of several AD-related genes in hippocampi without late AD-like pathogenesis and memory impairment in mice. Here, further studies on two low doses (5 or 10 cGy) of high LET carbonion irradiations are reported. On expression of 84 AD-related genes in hippocampi, at 4 hr after TBI, 5 cGy induced a significant upregulation of three genes (Abca1, Casp3, and Chat) and 10 cGy led to a marked upregulation of one gene (Chat) and a downregulation of three genes (Apoe, Ctsd, and Il1?), and, at 1 year after TBI, one gene (Il1?) was significantly downregulated in 10 cGy-irradiated animals. Changes in spatial learning ability and memory and induction of AD-like pathogenesis were not detected by in vivo brain imaging for amyloid-? peptide accumulation and by immunohistochemical staining of amyloid precursor protein, amyloid-? protein, tau, and phosphorylated tau protein. These findings indicate that low doses of carbon-ion irradiations did not cause behavioral impairment or AD-like pathological change in mice.
The cause and progression of Alzheimers disease (AD) are poorly understood. Possible cognitive and behavioral consequences induced by low-dose radiation are important because humans are exposed to ionizing radiation from various sources. Early transcriptional response in murine brain to low-dose X-rays (100 mGy) has been reported, suggesting alterations of molecular networks and pathways associated with cognitive functions, advanced aging and AD. To investigate acute and late transcriptional, pathological and cognitive consequences of low-dose radiation, we applied an acute dose of 100-mGy total body irradiation (TBI) with X-rays to C57BL/6J Jms mice. We collected hippocampi and analyzed expression of 84 AD-related genes. Mouse learning ability and memory were assessed with the Morris water maze test. We performed in vivo PET scans with (11)C-PIB, a radiolabeled ligand for amyloid imaging, to detect fibrillary amyloid beta peptide (A?) accumulation, and examined characteristic AD pathologies with immunohistochemical staining of amyloid precursor protein (APP), A?, tau and phosphorylated tau (p-tau). mRNA studies showed significant downregulation of only two of 84 AD-related genes, Apbb1 and Lrp1, at 4 h after irradiation, and of only one gene, Il1?, at 1 year after irradiation. Spatial learning ability and memory were not significantly affected at 1 or 2 years after irradiation. No induction of amyloid fibrillogenesis or changes in APP, A?, tau, or p-tau expression was detected at 4 months or 2 years after irradiation. TBI induced early or late transcriptional alteration in only a few AD-related genes but did not significantly affect spatial learning, memory or AD-like pathological change in mice.
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