The behavior of cells is generally considered to be regulated by environmental factors, but the molecules in the milieu of neural stem cells have been little studied. We found by immunohistochemistry that chondroitin sulfate (CS) existed in the surroundings of nestin-positive cells or neural stem/progenitor cells in the rat ventricular zone of the telencephalon at embryonic day 14. Brain-specific chondroitin sulfate proteoglycans (CSPGs), including neurocan, phosphacan/receptor-type protein-tyrosine phosphatase , and neuroglycan C, were detected in the ventricular zone. Neurospheres formed by cells from the fetal telencephalon also expressed these CSPGs and NG2 proteoglycan. To examine the structural features and functions of CS polysaccharides in the milieu of neural stem cells, we isolated and purified CS from embryonic day 14 telencephalons. The CS preparation consisted of two fractions differing in size and extent of sulfation: small CS polysaccharides with low sulfation and large CS polysaccharides with high sulfation. Interestingly, both CS polysaccharides and commercial preparations of dermatan sulfate CS-B and an E-type of highly sulfated CS promoted the fibroblast growth factor-2-mediated proliferation of neural stem/progenitor cells. None of these CS preparations promoted the epidermal growth factor-mediated neural stem cell proliferation. These results suggest that these CSPGs are involved in the proliferation of neural stem cells as a group of cell microenvironmental factors.
Since there are a plethora of studies on cadmium toxicity and poisoning in laboratory animals and humans, we have limited this review to studies that are relevant to human health issues by focusing on carcinogenicity, genotoxicity, circulatory disease, nephrotoxicity and life expectancy. Cadmium exposure has been established to induce cancer in various tissues of laboratory animals. Contrary to early findings of the lack of genotoxicity by cadmium, recent findings of mammalian cell culture studies have revealed genotoxic effects. Furthermore, cadmium exposure at relatively low doses induces circulatory diseases in laboratory animals. Despite such results of various cadmium toxicities in animal studies, data from human studies are lacking and insufficient to support the cause-effect relationship. Although cadmium is currently considered to be a human carcinogen by the International Agency for Research and Cancer, it is inappropriate to conclude that sufficient evidence on the carcinogenicity of cadmium in humans exists. It is also thought that epidemiological studies so far reported do not support the occurrence of cadmium-induced circulatory disease in humans. Since there are inconsistent reports on the relationship of cadmium exposure with the life expectancy of people living in cadmium-polluted areas, further studies are needed for clarification. It is also necessary to examine apparent discrepancies in result between humans and experimental animals. It has been established that long-term exposure to cadmium causes renal dysfunction in both humans and experimental animals, and whether there are any differences in the inducibility of metallothionein in the kidney warrants further study.
sleeping time by 1.8 to 8.0 times as compared with the control solution with 1% Tween 80-saline. The ED 50 values (mg/kg, i.v.) of 9α-OH-HHC and 8-OH-iso-HHC for the antinociceptive effect were 14.1 and 39.4, respectively. The present study demonstrated that CBD can be converted to ∆ 9 -THC and its related cannabinoids, 9α-OH-HHC and 8-OH-iso-HHC, in artifi cial gastric juice, and that these HHCs show ∆ 9 -THC-like effects in mice, although their pharmacological effects were less potent than those of ∆ 9 -THC.
Methylmercury (MeHg) modifies cellular proteins via their thiol groups in a process referred to as “S-mercuration”, potentially resulting in modulation of the cellular signal transduction pathway. We examined whether low-dose MeHg could affect Akt signaling involved in cell survival. Exposure of human neuroblastoma SH-SY5Y cells of up to 2 μM MeHg phosphorylated Akt and its downstream signal molecule CREB, presumably due to inactivation of PTEN through S-mercuration. As a result, the anti-apoptotic protein Bcl-2 was up-regulated by MeHg. The activation of Akt/CREB/Bcl-2 signaling mediated by MeHg was, at least in part, linked to cellular defence because either pretreatment with wortmannin to block PI3K/Akt signaling or knockdown of Bcl-2 enhanced MeHg-mediated cytotoxicity. In contrast, increasing concentrations of MeHg disrupted Akt/CREB/Bcl-2 signaling. This phenomenon was attributed to S-mercuration of CREB through Cys286 rather than Akt. These results suggest that although MeHg is an apoptosis-inducing toxicant, this environmental electrophile is able to activate the cell survival signal transduction pathway at lower concentrations prior to apoptotic cell death.
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