Deletion of the Selenocysteine tRNA Gene in Macrophages and Liver Results in Compensatory Gene Induction of Cytoprotective Enzymes by Nrf2
The selenocysteine tRNA (tRNASec) molecule is the sight of synthesis for the amino acid selenocysteine and the adaptor for its translational insertion into selenoprotein enzymes, the majority of which contribute to cellular redox homeostasis. To examine the consequences of selenoprotein depletion on the oxidative environment of the cell, we generated a conditional knock-out mouse for the tRNASec gene (Trsp). Deletion of Trsp in either macrophages or liver elevated oxidative stress and activated the of and and and of the of Trsp and the knock-out macrophages elevated oxidative and to of either gene a of Trsp on and a of Trsp selenoprotein is which is for cellular redox and The selenocysteine tRNA (tRNASec) molecule is the sight of synthesis for the amino acid selenocysteine and the adaptor for its translational insertion into selenoprotein enzymes, the majority of which contribute to cellular redox homeostasis. To examine the consequences of selenoprotein depletion on the oxidative environment of the cell, we generated a conditional knock-out mouse for the tRNASec gene (Trsp). Deletion of Trsp in either macrophages or liver elevated oxidative stress and activated the of and and and of the of Trsp and the knock-out macrophages elevated oxidative and to of either gene a of Trsp on and a of Trsp selenoprotein is which is for cellular redox and is for the and of and of of and of the to the of the in in the of amino acid is for The of selenocysteine a of and to of enzymes, a selenocysteine tRNA molecule (tRNASec) of the tRNASec gene in in and for liver of Trsp in is and liver to and of in for and in its the of the or to the of the is to the redox of the to a and which of and selenoprotein a and the enzymes, which in a and and redox in a of enzymes, and a of the Trsp gene to of a is the of is to the redox environment of the and to the oxidative to of the of to to selenoprotein a the of tRNASec a for of the selenocysteine in a of the majority of which elevated of a of oxidative stress the of enzymes, and in to oxidative stress or The to on a the and its is a of the of and is in and to the a of the a we a gene to the of the Trsp gene in mouse of the and in to the of we in to in the of selenoprotein is To in we a conditional knock-out mouse for the Trsp and gene of Trsp and and in to of gene and a oxidative selenoprotein is of the and of the conditional of a a into the of the tRNASec and a into the of the tRNASec a of the The for into the and a To of the the and a and of Trsp a into and to The or on and the for of for and a of the in the to the and in the to the of the of the Trsp gene in macrophages a of the for into the The of the and the gene the and of tRNASec and the of a of The a of and in and in a of the a of in a and to or or the of a a of the The of the and is the of the a of in for and of the and in for a to and of and and and in for and in for and for and macrophages the and The in and and for in a a of the of macrophages and and of and of the Trsp to cellular oxidative stress in the of selenoprotein we a conditional knock-out mouse for the Trsp The conditional a a which the Trsp gene and of the and of of which in the and the conditional Trsp a mouse of of the of the to of the in and the and the of the Trsp in and The the the of the of Trsp in and on tRNASec tRNASec in of of in a on mouse the for into the the of gene in of for macrophages and for to examine the of the Trsp in macrophages and in for and the is of in the the gene of the Trsp of and macrophages in and of the Trsp of the of Trsp is the a of or the of a of macrophages to of Trsp in macrophages and on tRNASec macrophages and for or and to the of the Trsp or to examine tRNASec the the cellular of tRNASec the of the Trsp the of tRNASec the of and of tRNASec which the and of tRNASec in macrophages for to and The in tRNASec is the of the tRNASec molecule is to the tRNA of a in tRNASec and the of in Trsp in the of and macrophages and the of macrophages the gene in we of macrophages for the selenoprotein and the of the in and in of tRNASec in a in and and and and of Trsp on and gene in and macrophages and for or or the macrophages and for or and for the of the The of Trsp in in and of for is or in we the of macrophages the the of is to the in of macrophages to and in the in and macrophages the in in of tRNASec and to on and on to the in of Trsp in macrophages in oxidative of the and is Deletion of the Trsp gene is to to of selenoprotein we the gene of a of and to oxidative The of and in macrophages to in of on to the of is a to for of selenoprotein and to the of cellular of in on the of to oxidative stress The on knock-out and Trsp to to the and for of To examine we generated macrophages and on either a or for and the of and the of macrophages a in the of is for the of in macrophages the of and the of in to of the of in macrophages of of on gene and in Trsp macrophages and on a or for and the of and the the macrophages of and for and the of and the macrophages the of and on a or and on the of the is of is its the of to or to to its to and in 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we to examine gene in a in selenoprotein To the Trsp gene liver in which the for is the of the to in the of and to in the for and in the in of in the of of gene of liver the of is a is to mouse of gene on of in and of The of the of and The the the of The and and the of and in the of of of the of the and in and of which is a knock-out of the of of the for the in the of selenoprotein and the of the Trsp gene in a of of the gene on and a for and the of of The to and and and and and and of liver and of in the of the of liver of in the of in the of or the of a into the the liver is in knock-out of in and the of knock-out a and of into the liver The and in or of liver of the in knock-out to and a in liver to the of in the of and the of knock-out of the gene mouse and liver contribute to the of cellular redox homeostasis. we for the the of selenoprotein is of the and which oxidative and on a cellular and The of and of the Trsp gene to a oxidative which the of the of the of and and the of the in The gene of a of the gene is in redox of the Trsp the of and which to of the selenoprotein to to oxidative and to a The of on of and the for and to to the for a and to oxidative a is the a to stress and is to the and in is its and to a of the the and is a for The a to of to the the the a and the the of the and to to the in the and of and the or the of the to is and is a for the a is of the of gene and and for gene in the of selenoprotein redox The gene is and selenoprotein is is the of the gene in to redox and to oxidative to the cellular redox of of which which the of the cell, and oxidative of in a of a of and of and in in which the of redox in the the gene is in the redox and oxidative the synthesis of and and the of and in the of the in its to the of oxidative stress the a in the of of and Trsp in liver and in of Trsp of the of the in a and the of gene is to the of the the of the of in of macrophages the which the to to the of to the in and redox The of and the gene macrophages to Trsp knock-out and the in of knock-out to Trsp knock-out to in knock-out and to oxidative of the to the of in of tRNASec the of and to of is the to the of or for and and the the of of for in the of in and to or gene in the the of a to is in the of mouse the of a in of to the of to the of oxidative and of for the of and of the gene in is of the knock-out of a of The of in Trsp we of gene the of is of the and and in to its is the of in and is of a environment the of the of the gene in and and the oxidative we in the of is activated a in the redox and of gene to and in to its in the gene is for the cellular redox which of or to is for the and of and of of and of the to the of the in in the of amino acid is for The of selenocysteine a of and to of enzymes, a selenocysteine tRNA molecule (tRNASec) of the tRNASec gene in in and for liver of Trsp in is and liver to and of in for and in its the of the or to the of the is to the redox of the to a and which of and selenoprotein a and the enzymes, which in a and The and redox in a of enzymes, and a of the Trsp gene to of a is the of is to the redox environment of the and to the oxidative to of the of to to selenoprotein a the of tRNASec a for of the selenocysteine in a of the majority of which elevated of a of oxidative stress the of enzymes, and in to oxidative stress or The to on a the and its is a of the of and is in and to the a of the a we a gene to the of the Trsp gene in mouse of the and in to the of we in to in the of selenoprotein is To in we a conditional knock-out mouse for the Trsp and gene of Trsp and and in to of gene and a oxidative selenoprotein is of the and of the conditional of a a into the of the tRNASec and a into the of the tRNASec a of the The for into the and a To of the the and a and of Trsp a into and to The or on and the for of for and a of the in the to the and in the to the of the of the Trsp gene in macrophages a of the for into the The of the and the gene the and of tRNASec and the of a of 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mouse for the Trsp The conditional a a which the Trsp gene and of the and of of which in the and the conditional Trsp a mouse of of the of the to of the in and the and the of the Trsp in and The the the of the of Trsp in and on tRNASec tRNASec in of of in a on mouse the for into the the of gene in of for macrophages and for to examine the of the Trsp in macrophages and in for and the is of in the the gene of the Trsp of and macrophages in and of the Trsp of the of Trsp is the a of or the of a of macrophages to the cellular of tRNASec the of the Trsp the of tRNASec the of and of tRNASec which the and of tRNASec in macrophages for to and The in tRNASec is the of the tRNASec molecule is to the tRNA of a in tRNASec and the of in Trsp in the of and macrophages and the of macrophages the gene in we of macrophages for the selenoprotein and the of the in and in of tRNASec in a in and and and and of Trsp on and gene in and macrophages and for or or the macrophages and for or and for the of the The of Trsp in in and of for is or in we the of macrophages the the of is to the in of macrophages to and in the in and macrophages the in in of tRNASec and to on and on to the in of Trsp in macrophages in oxidative of the and is Deletion of the Trsp gene is to to of selenoprotein we the gene of a of and to oxidative The of and in macrophages to in of on to the of is a to for of selenoprotein and to the of cellular of in on the of to oxidative stress The on knock-out and Trsp to to the and for of To examine we generated macrophages and on either a or for and the of and the of macrophages a in the of is for the of in macrophages the of and the of in to of the of in macrophages of of on gene and in Trsp macrophages and on a or for and the of and the the macrophages of and for and the of and the macrophages the of and on a or and on the of the is of is its the of to or to to its to and in the to the of macrophages of and for and the of to in the of macrophages macrophages of Trsp to the of the of is a cellular to for of selenoprotein in the of in macrophages on a a and a knock-out the the of or Trsp to in cellular the and of Trsp and the of in of either gene of the to the of Trsp and or in to of is the to oxidative the of and macrophages to or in Trsp and knock-out macrophages in and the of of macrophages to to macrophages a in to of in to the and the in the of the of Trsp and a in of either gene the the and to the of for cellular in the of selenoprotein the of macrophages and the the and of Trsp and and knock-out macrophages to and and macrophages on a or for or macrophages macrophages and and of macrophages the and to and in the in in macrophages and the in in to of selenoprotein to To or the of to the of the to the and The of Trsp in the in to in of Trsp and the of the the macrophages of in to on the gene the cellular the of the is to macrophages and to the of of or we to examine gene in a in selenoprotein To the Trsp gene liver in which the for is the of the to in the of and to in the for and in the in of in the of of gene of liver the of is a is to mouse of gene on of in and of The of the of and The the the of The and and the of and in the of of of the of the and in and of which is a knock-out of the of of the for the in the of selenoprotein and the of the Trsp gene in a of of the gene on and a for and the of of The to and and and and and and of liver and of in the of the of liver of in the of in the of or the of a into the the liver is in knock-out of in and the of knock-out a and of into the liver The and in or of liver of the in knock-out to and a in liver to the of in the of and the of knock-out of the gene mouse and liver of the Trsp to cellular oxidative stress in the of selenoprotein we a conditional knock-out mouse for the Trsp The conditional a a which the Trsp gene and of the and of of which in the and the conditional Trsp a mouse of of the of the to of the in and the and the of the Trsp in and The the the of the Deletion of Trsp in and on tRNASec tRNASec in of of in a on mouse the for into the the of gene in of for macrophages and for to examine the of the Trsp in macrophages and in for and the is of in the the gene of the Trsp of and macrophages in and of the Trsp of the of Trsp is the a of or the of a of macrophages to the cellular of tRNASec the of the Trsp the of tRNASec the of and of tRNASec which the and of tRNASec in macrophages for to and The in tRNASec is the of the tRNASec molecule is to the tRNA of a in tRNASec and the of in Trsp in the of and macrophages and the of macrophages the gene in we of macrophages for the selenoprotein and the of the in and in of tRNASec in a in and and and and Deletion of Trsp in in and of for is or in we the of macrophages the the of is to the in of macrophages to and in the in and macrophages the in in of tRNASec and to on and on to the in of Trsp in macrophages in oxidative of the and is Deletion of the Trsp gene is to to of selenoprotein we the gene of a of and to oxidative The of and in macrophages to in of on to the of is a to for of selenoprotein and to the of cellular of in on the of to oxidative stress The on knock-out and Trsp to to the and for of To examine we generated macrophages and on either a or for and the of and the of macrophages a in the of is for the of in macrophages the of and the of in to of the of in macrophages of The of is its the of to or to to its to and in the to the of macrophages of and for and the of to in the of macrophages macrophages of Trsp to the of the of is a cellular to for of selenoprotein in the of in macrophages on a a and a knock-out the the of or Trsp to in cellular the and of Trsp and the of in of either gene of the to the of Trsp and or in to of is the to oxidative the of and macrophages to or in Trsp and knock-out macrophages in and the of of macrophages to to macrophages a in to of in to the and the in the of the of Trsp and a in of either gene the the and to the of for cellular in the of selenoprotein the of macrophages and the the and in in macrophages and the in in to of selenoprotein to To or the of to the of the to the and The of Trsp in the in to in of Trsp and the of the the macrophages of in to on the gene the cellular the of the is to macrophages and to the of of or we to examine gene in a in selenoprotein To the Trsp gene liver in which the for is the of the to in the of and to in the for and in the in of in the of of gene of liver the of is a is to mouse of the and in and of which is a knock-out of the of of the for the in the of selenoprotein and the of the Trsp gene in a of in the of or the of a into the the liver is in knock-out of in and the of knock-out a and of into the liver The and in or of liver of the in knock-out to and a in liver to the of in the of and the of knock-out of the gene mouse and liver contribute to the of cellular redox homeostasis. we for the the of selenoprotein is of the and which oxidative and on a cellular and The of and of the Trsp gene to a oxidative which the of the of the of and and the of the in The gene of a of the gene is in redox of the Trsp the of and which to of the selenoprotein to to oxidative and to a The of on of and the for and to to the for a and to oxidative a is the a to stress and is to the and in is its and to a of the the and is a for The a to of to the the the a and the the of the and to to the in the and of and the or the of the to is and is a for the a is of the of gene and and of and in in which the of redox in the the gene is in the redox and oxidative the synthesis of and and the of and in the of the in its to the of oxidative stress the a in the of of and Trsp in liver and in of Trsp of the of the in a and the of gene is to the of the the of the of in of macrophages the which the to to the of to the in and redox The of and the gene macrophages to Trsp knock-out and the in of knock-out to Trsp knock-out to in knock-out and to oxidative of the to the of in of tRNASec the of and to of is the to the of or for and and the the of of for in the of in and to or gene in the the of a to is in the of mouse the of a in of to the of to the of oxidative and of for the of and of the gene in is of the knock-out of a of The of in Trsp we of gene the of is of the and and in to its is the of in and is of a environment the of the of the gene in and and the oxidative we in the of is activated a in the redox and of gene to and in to its in the gene is for the cellular redox which of or to contribute to the of cellular redox homeostasis. we for the the of selenoprotein is of the and which oxidative and on a cellular and The of and of the Trsp gene to a oxidative which the of the of the of and and the of the in The gene of a of the gene is in redox of the Trsp the of and which to of the selenoprotein to to oxidative and to a The of on of and the for and to to the for a and to oxidative a is the a to stress and is to the and in is its and to a of the the and is a for The a to of to the the the a and the the of the and to to the in the and of and the or the of the to is and is a for the a is of the of gene and and The of and in in which the of redox in the the gene is in the redox and oxidative the synthesis of and and the of and in the of the in its to the of oxidative stress the a in the of of and Trsp in liver and in of Trsp of the of the in a and the of gene is to the of the the of the of in of macrophages the which the to to the of to the in and redox The of and the gene macrophages to Trsp knock-out and the in of knock-out to Trsp knock-out to in knock-out and to oxidative The of the to the of in of tRNASec the of and to of is the to the of or for and and the the of of for in the of in and to or gene in the the of a to is in the of mouse the of a in of to the of to the of oxidative and of for the of and The of the gene in is of the knock-out of a of The of in Trsp we of gene the of is of the and and in to its is the of in and is of a environment the of the of the gene in and and the oxidative we in the of is activated a in the redox and of gene to and in to its in the gene is for the cellular redox which of or to and for and the of the of for