ライフサイエンスコーパス: GPx4

1 cally dependent on glutathione peroxidase 4 (GPX4).

2 id hydroperoxidase glutathione peroxidase 4 (GPX4).

3 that persister cells acquire a dependency on GPX4.

4 erozygous expression of catalytically silent Gpx4.

5 from mice specifically lacking mitochondrial Gpx4.

6 nocysteine insertion sequence element in the GPX4 3' untranslated region, and the rare allele of this

7 cules that inhibit glutathione peroxidase 4 (GPX4), a phospholipid peroxidase, cause lethal accumulat

8 on the phospholipid glutathione peroxidase (GPX4), a selenocysteine-containing enzyme that dissipate

9 spinal motor neuron degeneration induced by Gpx4 ablation exhibited features of ferroptosis, includi

10 neuron degeneration and paralysis induced by Gpx4 ablation suggest that ferroptosis inhibition by GPX

11 d in ferroptosis of motor neurons induced by Gpx4 ablation.

12 the onset of paralysis and death induced by Gpx4 ablation.

13 cient animals, the resulting males (Sec46Ala-Gpx4(+/-)+Alox15(-/-)) showed normalized fertility, and

14 Glutathione peroxidase 4 (GPX4), an antioxidant defense enzyme active in repairing

15 related genes, MnSOD, CuZnSOD, Nrf2, Keap1, GPx4 and Catalase was also examined.

16 le we created heterozygous animals (Sec46Ala-Gpx4(+/-)) and crossed them with Alox15 knock-out mice (

17 Glutathione peroxidase 4 (GPX4) and arachidonic acid 15-lipoxygenase (ALOX15) are

18 e dismutase (Sod), glutathione peroxidase 4 (Gpx4) and peroxiredoxin 3 (Prdx3) that render them susce

19 ause homozygous Gpx4 knock-in mice (Sec46Ala-Gpx4(+/+)) are not viable we created heterozygous animal

20 Consistent with the role of GPX4 as a ferroptosis inhibitor, spinal motor neuron deg

21 p15 and the glutathione peroxidases GPx1 and GPx4 being substantially reduced.

22 ozoa depends on the moonlighting function of Gpx4 both as an enzyme oxidizing capsular protein thiols

23 ther found that ferroptosis inducers inhibit GPX4 by covalently targeting the active site selenocyste

24 and total GPx activity, while knock-down of GPx4 by small interfering RNA (siRNA) increased VEGF, an

25 Together, TGR and GPx4 can serve as a novel disulfide bond formation syste

26 px4 is essential for mouse survival and that Gpx4 deficiency makes cells vulnerable to oxidative inju

27 might counteract male infertility related to GPX4 deficiency.

28 , ROS accumulation and lipid peroxidation in Gpx4-deficient cells remain high.

29 al T cell responses by using T cell-specific Gpx4-deficient mice.

30 Ex vivo, Gpx4-deficient T cells rapidly accumulated membrane lipi

31 GPx4 deletion reduces keratinocyte adhesion in culture a

32 tissues investigated, and overexpression of Gpx4 did not cause alterations in activities of glutathi

33 S died at the same embryonic stage (E7.5) as Gpx4(-/-) embryos as expected.

34 tightly controlled expression of functional Gpx4 emerges as a key for full male fertility.

35 ent during tumor promotion increased hepatic GPx4 expression and reduced the expression of VEGF and o

36 Selenium enhanced GPx4 expression and total GPx activity, while knock-down

37 to undergo ferroptosis because they sustain GPX4 expression, despite their increase in ACSL4.

38 n-specific CD8(+) and CD4(+) T cells lacking Gpx4 failed to expand and to protect from acute lymphocy

39 Here, we investigated the importance of Gpx4 for physiological T cell responses by using T cell-

40 e are dependent on the lipid hydroperoxidase GPX4 for survival.

41 These studies unveil an essential role of Gpx4 for T cell immunity.

42 Loss of GPX4 function results in selective persister cell ferrop

43 Notably, depletion of the Gpx4 gene in the memory phase of viral infection did not

44 thal phenotype of null mutation of the mouse Gpx4 gene, indicating that the transgene can replace the

45 ) using a genomic clone containing the human GPX4 gene.

46 de at the N terminus, are generated from the Gpx4 gene.

47 , we generated transgenic mice using mutated GPX4 genes encoding either the long form Gpx4 (lGPX4 gen

48 ial showed that SNPs can affect responses of GPx4, GPx1 and GPx3 protein expression or activity in re

49 utation of the active site selenocysteine of Gpx4 (Gpx4_U46S).

50 dative damage repair (CAT, SOD1, SOD2, GPX1, GPX4, GSR, TXN, TXN2, TXNRD1, and TXNRD2) and survival i

51 tion of common variants in SOD1, SOD2, GPX1, GPX4, GSR, TXNRD1, and TXN2.

52 Endothelium-specific deletion of Gpx4 had no obvious impact on normal vascular homeostasi

53 Yet a role of Gpx4 in endothelial cell function has remained enigmatic

54 We show that mice with deletion of Gpx4 in hematopoietic cells develop anemia and that Gpx4

55 gene can replace the essential role of mouse Gpx4 in mouse development.

56 Conditional ablation of Gpx4 in neurons of adult mice resulted in rapid onset an

57 of phospholipid hydroperoxide-specific GPx (GPx4) in NIH/3T3 cells led to increases in cellular pero

58 eration and the pharmacological mechanism of GPX4 inhibition that generates ROS in lipid environments

59 Thus, GPX4 is an essential regulator of ferroptotic cancer cel

60 for the hypothesis that common variation in GPX4 is associated with prognosis after a diagnosis of b

61 a chemoproteomics strategy to discover that GPX4 is directly inhibited by a second class of compound

62 The selenoenzyme Gpx4 is essential for early embryogenesis and cell viabi

63 ation suggest that ferroptosis inhibition by GPX4 is essential for motor neuron health and survival i

64 Here we show that GPX4 is essential for motor neuron health and survival i

65 Our previous studies showed that Gpx4 is essential for mouse survival and that Gpx4 defic

66 hematopoietic cells develop anemia and that Gpx4 is essential for preventing receptor-interacting pr

67 is sufficient to trigger ferroptosis because GPX4 is suppressed.

68 antioxidant enzyme glutathione peroxidase 4 (Gpx4) is a key regulator of oxidative stress-induced cel

69 The selenoenzyme glutathione peroxidase 4 (Gpx4) is a major scavenger of phospholipid hydroperoxide

70 Glutathione peroxidase 4 (Gpx4) is an essential antioxidant enzyme having multiple

71 The selenoenzyme glutathione peroxidase 4 (Gpx4) is an intracellular antioxidant enzyme important f

72 Glutathione peroxidase 4 (Gpx4) is uniquely involved in the detoxification of oxid

73 Because homozygous Gpx4 knock-in mice (Sec46Ala-Gpx4(+/+)) are not viable w

74 To address this question we employed Gpx4 knock-in mice expressing the Sec46Ala-Gpx4 mutant,

75 t, aortic explants from endothelium-specific Gpx4 knockout mice showed a markedly reduced number of e

76 upregulated in the skin and keratinocytes of GPx4-knockout mice.

77 Absence of Gpx4 leads to functional inactivation of caspase 8 by gl

78 ciency or dysfunction of a selenoperoxidase, GPX4, leads to ferroptosis.

79 ted GPX4 genes encoding either the long form Gpx4 (lGPX4 gene) or the short form Gpx4 (sGPX4 gene).

80 a normal phenotype in resting skin, whereas GPx4 loss in the epidermis caused epidermal hyperplasia,

81 These findings suggest that targeting of GPX4 may represent a therapeutic strategy to prevent acq

82 lizes the reduced fertility of male Sec46Ala-Gpx4(+/-) mice by improving the motility of their sperm.

83 When Sec46Ala-Gpx4(+/-) mice were crossed with Alox15-deficient animal

84 Male Sec46Ala-Gpx4(+/-) mice, but not their female littermates, were s

85 less in murine embryonic fibroblasts from Tg(GPX4) mice compared with wild type mice.

86 s of transgenic mice overexpressing Gpx4 (Tg(GPX4) mice) using a genomic clone containing the human G

87 diquat-induced apoptosis was decreased in Tg(GPX4) mice, as evidenced by attenuated caspase-3 activat

88 Both lines of Tg-(GPX4) mice, Tg5 and Tg6, had elevated levels of Gpx4 (mR

89 d by diquat were reduced significantly in Tg(GPX4) mice.

90 there were no differences in total levels of GPX4 mRNA across genotypes.

91 4) mice, Tg5 and Tg6, had elevated levels of Gpx4 (mRNA and protein) in all tissues investigated, and

92 d Gpx4 knock-in mice expressing the Sec46Ala-Gpx4 mutant, in which the catalytic selenocysteine was r

93 Interestingly, the male Gpx4-null mice rescued by the sGPX4 gene were infertile

94 In Gpx4-null mice rescued by the sGPX4 gene, the Gpx4 prote

95 to rescue the lethal phenotype of the mouse Gpx4-null mutation.

96 to rescue the lethal phenotype of the mouse Gpx4-null mutation.

97 one peroxidase family (GPX1, GPX2, GPX3, and GPX4), one or more iodothyronine deiodinases and two thi

98 lacking either the glutathione peroxidase 4 (GPx4) or thioredoxin reductase 1 (TR1) gene were generat

99 Ectopic GPx4 overcame this, reduced peroxidized phospholipid acc

100 GPX4 overexpression and knockdown modulated the lethalit

101 the sperm, including glutathione peroxidase GPx4/PHGPx.

102 These data demonstrate that Gpx4 plays a role in vivo in the mechanism of apoptosis

103 nhibition of the catalytic selenocysteine in Gpx4 prevents elimination of PUFA hydroperoxides; these

104 A long form Gpx4 protein and a short form Gpx4 protein, which are di

105 genic mice with the sGPX4 gene had increased Gpx4 protein in all tissues and were protected against d

106 submitochondrial distribution pattern of the Gpx4 protein in these mice was identical to that in wild

107 nst apoptosis in mice, whereas the long form Gpx4 protein is important for male fertility.

108 rated for the first time that the short form Gpx4 protein is present in somatic tissue mitochondria a

109 genic mice with the lGPX4 gene had increased Gpx4 protein only in the testes, and the lGPX4 gene fail

110 px4-null mice rescued by the sGPX4 gene, the Gpx4 protein was present in mitochondria isolated from s

111 A long form Gpx4 protein and a short form Gpx4 protein, which are distinguishable by the presence

112 tion of all selenoproteins, mice ablated for GPx4 recovered after 5 weeks and had a normal life span.

113 l carcinomas are particularly susceptible to GPX4-regulated ferroptosis.

114 Although Gpx4 represents a key component of the reactive oxygen s

115 droperoxide glutathione peroxidase (PHGPX or GPX4), respectively.

116 GPX4 rs713041 is located near the selenocysteine inserti

117 wo single nucleotide polymorphisms (SNPs) in GPX4 (rs713041 and rs757229) were associated with all-ca

118 enoprotein gene expression, in particular in GPx4, SelK, SelM, SelW, and Sep15.

119 m both enzymes are apparently expressed, and GPX4 serves as anti-oxidative enzyme but also as a struc

120 ong form Gpx4 (lGPX4 gene) or the short form Gpx4 (sGPX4 gene).

121 GPx4 silencing led to 2-4-fold increases in PG-G formati

122 Conversely, GPx4 siRNA knockdown enhanced phospholipid peroxidation,

123 ow for the first time that in the absence of Gpx4, sufficient vitamin E supplementation is crucial fo

124 two lines of transgenic mice overexpressing Gpx4 (Tg(GPX4) mice) using a genomic clone containing th

125 These data link the activity of cutaneous GPx4 to the regulation of COX-2 and hair follicle morpho

126 teins involved in antioxidant defense (Gpx1, Gpx4, TR1, SelS, SelK, and Sps2).

127 The human GPX4 transgene rescued the lethal phenotype of null muta

128 Five selenoproteins (Gpx4, Txnrd1, Txnrd2, Dio3, and Sepp1) were classified a

129 Dependency on GPX4 was found to exist across diverse therapy-resistant

130 Recently, the cytosolic form of Gpx4 was identified as an upstream regulator of a novel

131 t for 6 weeks before endothelial deletion of Gpx4 was induced by 4-hydroxytamoxifen.

132 ptosis, whereas the mitochondrial isoform of Gpx4 was previously shown to be crucial for male fertili

133 d by inhibition of glutathione peroxidase 4 (GPX4), which catalyzes the reduction of lipid peroxides

134 on was mediated by glutathione peroxidase 4 (GPx4), which preferentially degrades lipid peroxides.

135 Glutathione peroxidase-4 (GPx4), which specifically metabolizes lipid hydroperoxid