Germ cell-specific nucleocytoplasmic shuttling protein, tesmin, responsive to heavy metal stress in mouse testes

Matsuura, Tadashi; Kawasaki, Yushi; Miwa, Keiko; Sutou, Shizuyo; Ohinata, Yasuhide; Yoshida, Fumiko; Mitsui, Youji

doi:10.1016/s0162-0134(01)00377-4

Cited by 30 publications

(30 citation statements)

References 34 publications

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“…It has been reported that male germ cells contain a cysteine-rich and MT-homologous protein, tesmin (Sugihara et al, 1999). Tesmin is also localized in the nuclei on meiosis during spermatogenesis or with various stimuli (Matsuura et al, 2002). These results suggest that MT acts as a nuclear antioxidant against feeble ROS, which are generated with progression of the cell cycle.…”

Section: Discussionmentioning

confidence: 83%

Nuclear trafficking of metallothionein requires oxidation of a cytosolic partner

Takahashi

Ogra

Suzuki

2004

Journal Cellular Physiology

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The present study revealed the mechanism underlying the nuclear trafficking of metallothionein (MT). Nuclear localization of MT in digitonin-permeabilized BALB 3T3 cells was enhanced in the presence of a cytosolic factor added as a rat red blood cell lysate by oxidation with H2O2 in a dose-dependent manner, but inhibited with excess glutathione. A cytosolic partner was assumed to bind MT and retain it in the cytoplasm, and its oxidation can mobilize MT to the nuclei on cellular oxidation. Pre-treatment of nuclei with H2O2 did not enhance the localization, and MT that had been localized in the nuclei was washed out, indicating that MT is in the nuclei as a result of a higher rate of uptake by the nuclei than the rate of diffusion from the nuclei. Nuclear localization of lysozyme and nuclear localization signal (NLS)-bearing allophycocyanin were not enhanced by the oxidation in the presence of cytosolic factor, suggesting that the nuclear traffic occurring on oxidation is specific to MT. Moreover, when cells were arrested the cell cycle at the S phase, MT was localized in the nuclei in response to coincidental generation of a feeble reactive oxygen species (ROS). These observations suggest that MT comes localized in the nuclei on the sensing of intracellular oxidation, whereby a cytosolic partner specific to MT comes oxidized as a cargo system, MT being localized as a result of enhanced uptake in the nuclei and re-localized in the cytoplasm diffusely. Nuclear MT was proposed to protect the nuclei from the oxidation occurring with progression of the cell cycle.

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Section: Discussionmentioning

confidence: 83%

Nuclear trafficking of metallothionein requires oxidation of a cytosolic partner

Takahashi

Ogra

Suzuki

2004

Journal Cellular Physiology

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“…The most significantly matching metallothionein-like gene models in T. pseudonana were similar to tesmin, which is a metal-binding transcription factor (29). Similarity searches against the T. pseudonana genome using several described plant and fungal (14) and in the diatom T. weissflogii (1).…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Induced by Copper Stress in the DiatomThalassiosira pseudonana

2006

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Utilizing a PCR-based subtractive cDNA approach, we demonstrated that the marine diatom Thalassiosira pseudonana exhibits a rapid response at the gene level to elevated concentrations of copper and that this response attenuates over 24 h of continuous exposure. A total of 16 copper-induced genes were identified, 11 of which were completely novel; however, many of the predicted amino acid sequences had characteristics suggestive of roles in ameliorating copper toxicity. Most of the novel genes were not equivalently induced by H 2 O 2 -or Cd-induced stress, indicating specificity in response. Two genes that could be assigned functions based on homology were also induced under conditions of general cellular stress. Half of the identified genes were located within two inverted repeats in the genome, and novel genes in one inverted repeat had mRNA levels induced by ϳ500-to 2,000-fold by exposure to copper for 1 h. Additionally, some of the inverted repeat genes demonstrated a dose-dependent response to Cu, but not Cd, and appear to belong to a multigene family. This multigene family may be the diatom functional homolog of metallothioneins.Copper (Cu) is an essential micronutrient required as a redox cofactor in a number of enzymes, including cytochrome oxidase, plastocyanin, and Cu/Zn superoxide dismutase. However, due to the redox chemistry of Cu, it is a potent toxin at elevated concentrations, and organisms utilize homeostatic mechanisms to tightly control both the intracellular concentration and activity of Cu (26).One means of Cu detoxification includes the synthesis of metal-binding ligands. The primary types of described metalbinding ligands are metallothioneins and phytochelatins, which are cysteine-rich protein molecules found in the plant and animal kingdoms (9), with metallothioneins also occurring in the prokaryotic genus Synechococcus (36). The amino acid sequences of metallothioneins are gene encoded, while phytochelatins are enzymatically produced by phytochelatin synthase. Although both of these ligands have important roles in metal detoxification, additional functions have not been ruled out, including roles in essential metal ion homeostasis. (For a review of phytochelatins and metallothioneins, see reference 9.)

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“…Indeed, it has been reported that male germ cells contain cysteine-rich and MT-homologous protein, tesmin. 22) Tesmin is also localized in the nuclei on meiosis during spermatogenesis or with various stresses, 23) suggesting that it acts as a nuclear antioxidant against endogenous ROS and compensates for the role of MT even in MT-/-cells.…”

Section: Resultsmentioning

confidence: 99%

Role of Metallothionein in the Cell Cycle: Protection against the Retardation of Cell Proliferation by Endogenous Reactive Oxygen Species

Takahashi

Ogra

Ibata

et al. 2004

JOURNAL OF HEALTH SCIENCE

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The growth rate of metallothionein (MT)-null (MT-/-) cells was significantly lower than that of wild-type (MT+/+) cells, the cell cycle being arrested at the G 2 /M phase in MT-/-cells and endogenous reactive oxygen species (ROS) accumulating with the progress of the cell cycle. Exogenous ROS generated on treatment with H 2 O 2 arrested the cell cycle of MT-/-cells at the G 2 /M phase more severely than that of MT+/+ cells. These observations suggest that MT maintains the normal cell cycle as an antioxidant against excessive endogenous ROS that are generated synchronously with the cell cycle and disturb the normal cell cycle.

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Germ cell-specific nucleocytoplasmic shuttling protein, tesmin, responsive to heavy metal stress in mouse testes

Cited by 30 publications

References 34 publications

Nuclear trafficking of metallothionein requires oxidation of a cytosolic partner

Nuclear trafficking of metallothionein requires oxidation of a cytosolic partner

Gene Expression Induced by Copper Stress in the DiatomThalassiosira pseudonana

Role of Metallothionein in the Cell Cycle: Protection against the Retardation of Cell Proliferation by Endogenous Reactive Oxygen Species

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