Seryl-tRNA synthetase (SerRS) is a class-2 aminoacyl-tRNA synthetase that catalyzes serine activation and its transfer to tRNA^Ser. The enzyme also serylates tRNA^Sec and thus participates in the incorporation of selenocysteine into selenoproteins. Methanogenic archaea possess unusual SerRS evolutionarily distinct from those found in other archaea, eukaryotes, and bacteria. The core three motifs and an active site are conserved in all SerRSs, whereas methanogenic archaeal SerRS has a unique N-terminal domain, which includes a tRNA-binding site. Here, we show evidence that Methanocaldococcus jannaschii seryl-tRNA synthetase (mjSerRS) catalyzes the formation of phosphoseryl-tRNA^Sec (PSer-tRNA^Sec) from serine, tRNA^Sec, and ATP. In vitro analyses revealed that M. jannaschii tRNA^Sec was charged with serine and then converted to PSer-tRNA^Sec by mjSerRS. Furthermore, selenocysteyl-tRNA^Sec (Sec-tRNA^Sec) was synthesized in an in vitro reaction with mjSerRS, selenocysteine synthase, and tRNA^Sec in the absence of seryl-tRNA kinase, which has been proposed as a key enzyme in Sec-tRNA^Sec synthesis in eukaryotes and archaea. Sequence analysis revealed that the N-terminal region of mjSerRS is similar to the entire sequence of M. jannaschii seryl-tRNA kinase. These results suggest that the N-terminus of mjSerRS is responsible for the phosphorylation of seryl-tRNA^Sec.

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Zinc is released from glutamatergic (zincergic) neuron terminals in the hippocampus, followed by the increase in Zn²⁺ concentration in the intracellular (cytosol) compartment, as well as that in the extracellular compartment. The increase in Zn²⁺ concentration in the intracellular compartment is mainly due to Zn²⁺ influx through calcium-permeable channels, while other organelles including the cytoplasm may be also involved in its increase. The increase in Zn²⁺ concentration in both compartments serves as Zn²⁺ signaling and modulates neuronal activity. Zn²⁺ serves as a negative feedback factor against presynaptic activity (glutamate release) and may participate in synaptic plasticity ; Zn²⁺ attenuates long-term potentiation (LTP) at mossy fiber synapses, while potentiates LTP at Schaffer collateral/commissural synapses. This paper summarizes that synaptic Zn²⁺ homeostasis is critical for hippocampus function and may be disturbed after exposure to acute stress. Significance of this disturbance is discussed.

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Zinc is believed to modulate neurotransmitters such as glutamate and GABA in the central nervous system (CNS). Metallothioneins (MTs) aid in heavy metal metabolism and detoxification, and protect CNS cells from numerous pathologies. However, little is known about neurobehavioral significance of MTs or their relationship with zinc. To understand the effect of MT-I and MT-II (MT-I, II) on behavioral function and to elucidate the relationship between zinc and MT-I, II, we performed neurobehavioral tests on female MT-I, II knockout mice established from a 129/Sv strain (MT null) and their control (wild-type) counterparts. Five-week-old mice of both strains were divided into two groups of zinc-deficient (Zn-) or -supplemented (Zn+) diet. Four weeks after initiating the experimental diet, the following tests were performed : measurement of 24-h spontaneous motor activities, open-field test, and Morris water maze. Growth of both strains was suppressed by feeding the mice with a Zn- diet. We observed lower zinc levels in the liver and kidney in both MT null groups with no significant difference between mice strains. Various spontaneous activity patterns were observed between MT null and wild-type (WT) mice. In the first phase of the Morris water maze, zinc deficiency caused significantly prolonged latency in the MT null mice. Nearly identical decreases in brain zinc levels were observed in MT null and WT mice after consuming the Zn- diet, and treatment of Zn deficiency in MT null mice impaired the formation of spatial learning memory. These findings suggest that MT-I, II play a role in modulating behavioral activities, and that zinc is essential for the spatial cognitive function of MTs.

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To clarify the effect of polaprezinc (a chelate compound consisting of zinc ion and L-carnosine) on taste disorder, we investigated the effect of polaprezinc on zinc-deficient (Zn(-)) diet-induced hypogeusia model in rats. After four weeks on the Zn(-) diet feeding, polaprezinc (1, 3 or 10mg/kg) for four weeks or [⁶⁵Zn] polaprezinc (10mg/kg) for two weeks were administered orally once a day. Zn(-) rats increased the preference rate for quinine hydrochloride solution, while polaprezinc repaired the increased taste preference rate. We also evaluated the proliferation of taste bud cells in the circumvallate papilla using 5-bromo-2'-deoxyuridine (BrdU). The incorporation of BrdU into taste bud cells in Zn(-) rats was reduced as compared with that in zinc-sufficient (Zn(+)) rats and polaprezinc at doses of 3 and 10mg/kg improved the reduced incorporation of BrdU into taste bud cells. The zinc concentration in the lingual epithelium was markedly decreased in Zn(-) rats as compared with Zn(+) rats. After administration of polaprezinc to Zn(-) rats at doses of 1, 3 and 10mg/kg, zinc concentration in the lingual epithelium significantly increased. Moreover, after administration of [⁶⁵Zn] polaprezinc, the ⁶⁵Zn radioactivity was mainly detected in the epithelium of the tongue in Zn(-) rats. These findings are indicating that the altered taste preferences by zinc deficiency is induced by the delayed proliferation of taste bud cells, and the restoration of zinc contents by polaprezinc in the lingual epithelium repaired the increased taste preference rate by improving the delay of cell proliferation. The results demonstrate the significance of zinc and the therapeutic efficacy of polaprezinc for taste disorder.

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Recent increase in the use of cadmium nitrate Cd (NO₃)₂ (CdN) in nickel cadmium batteries means that workers at factories producing these batteries are at risk of frequent inhalation of CdN aerosols. We aimed to investigate the subacute harmful effects towards the lungs, liver, and kidneys after intermittent inhalation and biological monitoring of cadmium (Cd). Three doses of CdN and saline (control) were intratracheally administered to rats ten times during three weeks using an aerosol generator. Blood, bronchoalveolar lavage fluid (BALF), and lung tissues were sampled. Blood parameters indicated severe hypoxemia. Pathohistological findings of the CdN group indicated typical, though non-specific changes such as tissue-destructive processes, occupation of the alveolar region, proliferation-associated changes, and extensive deformities of alveolar architecture. Increased LDH and surfactant protein-D in BALF were suspected to be due to injurious effects and hyperplasia of the type- II pneumocytes. Blood Cd concentrations and BALF suggest that the absorbed dose was much lower than that of fatal cases following acute inhalation accidents. In a previous study, we defined serum levels of Cd at which no mortality and no abnormalities in the liver and kidneys were observed. However, it is generally reported that toxicity to the respiratory system is proportional to the time and level of exposure. Thus, subacute lethal effects were suspected to increase despite the minimal dose used in the present study, as repeated inhalation exposure and length of contact with Cd would yield severe pathohistological changes. Morphological abnormalities could also be responsible for the significant decrease in arterial blood gas values in this study. The marked pathologic change in the lungs, diagnosed as diffuse alveolar damage, was likely caused by repeated inhalation exposure of Cd. Subacute lung damage which worsened for a few days was lethal.

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