ライフサイエンスコーパス: CypD

1 CypD activity also correlated with synthasome assembly i

2 CypD enhances the limiting effect of Bcl2 on the tBid-in

3 CypD knockout mice also presented accelerated wound heal

4 CypD loss triggers a metabolic shift in Ppif-/- male and

5 CypD was upregulated in HD patients, and this upregulati

6 CypD(-/-) mice developed a less-severe form of pancreati

7 CypD-deficient platelets exhibited defects in phosphatid

8 CypD-deficient primary mouse embryonic fibroblasts (MEFs

9 CypD-dependent proteolytic events, including cleavage of

10 the role of CypD in cell death, we created a CypD-deficient mouse.

11 ion, and platelet procoagulant activity in a CypD-dependent manner.

12 This activates CypD's isomerase activity.

13 he reported role of CypD in mPTP activation, CypD null (CypD(-/-)) MEFs exhibited significantly less

14 Our study finds that catalytically active CypD causes strong aggregation of wild-type p53 protein

15 tors of cyclophilins and tested them against CypD using binding and isomerase activity assays.

16 Tomm40 (translocase of outermembrane 40) and CypD (cyclophilin D) in grade III and grade IV HD patien

17 The increase in Drp1, Fis1 and CypD and the decrease in Mfn1 and Mfn2 may be responsibl

18 rotein levels of Drp1 and Fis1 (fission) and CypD (matrix) genes, and increased levels of Mfn1, Mfn2

19 bility transition pore opening in a p53- and CypD-dependent manner.

20 igomeric complex composed of VDAC, SPG7, and CypD.

21 ls of pancreatitis, induced in wild-type and CypD(-/-) mice by a combination of ethanol and CCK.

22 ated cardiac mitochondria from wild-type and CypD(-/-) mice to immunoprecipitation using agarose bead

23 ptides that were acetylated in wild-type and CypD(-/-) samples and found 11 peptides (10 proteins) de

24 d heart mitochondria from wild-type (WT) and CypD knockout (KO) mice were treated to either stimulate

25 rotective chaperone network that antagonizes CypD-dependent cell death in tumors.

26 poxia-reoxygenation, the interaction between CypD and the IP3R1 Ca(2+) channeling complex increased c

27 n2 similarly reduced the interaction between CypD and the IP3R1 complex and protected against hypoxia

28 of the F1F0 ATP synthase-CypD interaction by CypD ablation protected against diabetes-induced mPTP op

29 ion, we infected CypD(-/-) MEFs with a C203S-CypD vector.

30 cted a recombinant adenovirus encoding C203S-CypD or WT CypD into CypD(-/-) mice via tail vein.

31 s of CypD(-/-) mice or mice expressing C203S-CypD were resistant to Ca(2+)-induced swelling as compar

32 To determine whether mutation of C203S-CypD would alter mPTP in vivo, we injected a recombinant

33 Surprisingly, C203S-CypD reconstituted MEFs were resistant to mPTP opening i

34 e the mitochondrial chaperone cyclophilin D (CypD) and trigger permeability transition pore opening,

35 Cyclophilin D (CypD) appears to be a critical component of the PTP.

36 ER-000444793 neither affected cyclophilin D (CypD) enzymatic activity, nor displaced of CsA from CypD

37 Cyclophilin D (CypD) is a mitochondrial immunophilin and a key positive

38 Cyclophilin D (CypD) is a mitochondrial matrix peptidyl-prolyl isomeras

39 mitochondrial matrix protein cyclophilin D (CypD) is an essential component of the mitochondrial per

40 le within ATP synthase is the cyclophilin D (CypD) regulated mitochondrial permeability transition po

41 p60) directly associates with cyclophilin D (CypD), a component of the mitochondrial permeability tra

42 Cells deficient in cyclophilin D (CypD), a component of the MPTP, are resistant to MPTP op

43 ve shown that cysteine 203 of cyclophilin D (CypD), a critical mPTP mediator, undergoes protein S-nit

44 d at inhibiting mitochondrial cyclophilin D (CypD), a key regulator of the mPT, as a potential therap

45 he mitochondrial MAM protein, cyclophilin D (CypD), altered insulin signaling in mouse and human prim

46 In the absence of cyclophilin D (CypD), an essential regulator of MPTP formation, murine

47 permeability transition pore, cyclophilin D (CypD), influenced endothelial metabolism and intracellul

48 ingle-channel patch clamp and cyclophilin D (CypD)-deficient mice (Ppif (-/-)) with streptozotocin-in

49 report an unexplored role of cyclophilin D (CypD)-dependent mitochondrial permeability transition po

50 tivates the key mPT regulator cyclophilin D (CypD).

51 pore permeability regulator, Cyclophilin D (CypD).

52 is impaired in the absence of cyclophilin D (CypD).

53 action with the PTP regulator cyclophilin D (CypD).

54 or reduction in the levels of cyclophilin D (CypD, also called Ppif), a mitochondrial matrix peptidyl

55 Cyclophilin D (CypD, encoded by Ppif) is an integral part of the mitoch

56 Ca(2+) retention, similar to cyclophilin D (CypD, PPIF) knockdown with sustained DeltaPsim during bo

57 The peptidylprolyl isomerase, cyclophilin D (CypD, PPIF), is a positive regulator of the pore, and ge

58 Inhibition of either CypD, IP3R1, or Grp75 decreased protein interaction with

59 resent a new proline isomerization assay for CypD by monitoring the aggregation of p53 as an indicato

60 n, strongly supporting an essential role for CypD in an ischemic injury model in which calcium overlo

61 These results implicate a role for CypD in modulating protein acetylation.

62 nzymatic activity, nor displaced of CsA from CypD protein, suggesting a mechanism independent of CypD

63 ent endothelial cells and aortic tissue from CypD knockout mice exhibited a dramatic increase in angi

64 Functionally, CypD-deficient endothelial cells and aortic tissue from

65 is1 (fission), Mfn1, Mfn2 and Opa1 (fusion), CypD (matrix), mitochondrial biogenesis-Nrf1, Nrf2, PGC1

66 The matrix gene CypD was up-regulated in AD patients.

67 We, therefore, generated CypD-RIPK3 double-deficient mice that are viable and fer

68 However, CypD-deficient MEFs were significantly less susceptible

69 These results implicate CypD and the MPTP as critical regulators of platelet act

70 th induced by hydrogen peroxide, implicating CypD in oxidative stress-induced cell death.

71 Importantly, CypD-deficient mice displayed a dramatic reduction in br

72 jury, thrombosis was markedly accelerated in CypD-deficient mice.

73 Also, in CypD-deficient platelet-rich plasma, clot retraction was

74 ht play a role in these metabolic changes in CypD(-/-) hearts.

75 d and 96 peptides (48 proteins) increased in CypD(-/-) samples.

76 ibute to altered mitochondrial metabolism in CypD(-/-) mice.

77 sed synthasome disassembly in WT, but not in CypD KO heart mitochondria.

78 ed by MPTP because they were not observed in CypD(-/-) acinar cells.

79 id oxidation that was previously reported in CypD(-/-) hearts, we measured the activity of l-3-hydrox

80 is required for this protection, we infected CypD(-/-) MEFs with a C203S-CypD vector.

81 indirectly activates the normally inhibited CypD by displacing it from Trap1 complexes.

82 enovirus encoding C203S-CypD or WT CypD into CypD(-/-) mice via tail vein.

83 These findings provide new insights into CypD-dependent mitochondrial mPTP and signaling on mitoc

84 hanisms of the protective effects of lacking CypD on Abeta-induced abnormal mitochondrial transport i

85 Liberated CypD then isomerizes multiple proteins including p53 (ca

86 Similarly, genetic ablation of mitochondrial CypD in Ppif-null mice did not afford protection from AP

87 In summary, loss of mitochondrial CypD results in a shift in bioenergetics and in activati

88 of a nitric oxide donor, GSNO, to WT but not CypD(-/-) MEFs prior to H(2)O(2) attenuated mPTP opening

89 Notably, CypD deficiency substantially improves learning and memo

90 bbeta3 inactivation, and demonstrate a novel CypD-dependent negative feedback mechanism that limits p

91 s of platelet activation and suggest a novel CypD-dependent negative-feedback mechanism regulating ar

92 Here we identified a novel, CypD-independent inhibitor of the mPTP.

93 role of CypD in mPTP activation, CypD null (CypD(-/-)) MEFs exhibited significantly less mPTP openin

94 mPTP activation, we mutated cysteine 203 of CypD to a serine residue (C203S) and determined its effe

95 ther, these results suggest that ablation of CypD leads to changes in the mitochondrial acetylome, wh

96 d to map acetylation sites after ablation of CypD, we subjected tryptic digests of isolated cardiac m

97 Furthermore, the absence of CypD alleviated deficits in synaptic plasticity, learnin

98 Furthermore, the absence of CypD protects neurons from Abeta- and oxidative stress-i

99 In the absence of CypD, active STAT3 enhances cell proliferation via accel

100 In the absence of CypD, integrin alphaIIbbeta3 function was accentuated in

101 not be critically involved in the absence of CypD.

102 d cell injury predominates in the absence of CypD.

103 Blockade of CypD may be a therapeutic strategy in Alzheimer's diseas

104 bute to malignant traits under conditions of CypD modulation.

105 mice with a platelet-specific deficiency of CypD.

106 XPHOS, inhibition of the PTP, or deletion of CypD increased high order synthasome assembly.

107 bly, blockade of mPTP by genetic deletion of CypD suppresses Abeta-mediated activation of the p38 mit

108 cological inhibition or genetic depletion of CypD and that peroxynitrite-mediated cell injury predomi

109 Depletion of CypD significantly protects axonal mitochondrial motilit

110 models in mice suggested the distinctness of CypD-mediated MPT from RIPK1/RIPK3-mediated necroptosis.

111 from mitochondria and that such an effect of CypD is cyclosporine A- and Bcl2-dependent.

112 pothesized that the anti-apoptotic effect of CypD is independent of the MPT but is due to its interac

113 Here we characterized the effects of CypD ablation on bioenergetics in the kidney.

114 Diabetes-induced elevation of CypD triggers enhancement of F1F0 ATP synthase-CypD inte

115 refore, we here describe a novel function of CypD as a Bcl2 collaborator and an inhibitor of cytochro

116 This function of CypD may explain the anti-apoptotic effect of this prote

117 otein, suggesting a mechanism independent of CypD inhibition.

118 ng the aggregation of p53 as an indicator of CypD activity.

119 on revealed selective cellular inhibition of CypD and the permeability transition pore with reduced c

120 Genetic or pharmacological inhibition of CypD in both H9c2 cardiomyoblasts and adult cardiomyocyt

121 Genetic or pharmacological inhibition of CypD provided a similar effect in adult mice cardiomyocy

122 Here we show that interaction of CypD with mitochondrial amyloid-beta protein (Abeta) pot

123 llular level, overexpression or knockdown of CypD respectively decreases or increases cytochrome c re

124 Mitochondria isolated from livers of CypD(-/-) mice or mice expressing C203S-CypD were resist

125 aim was to test the hypothesis that loss of CypD alters the cardiac mitochondrial acetylome.

126 kt were also noted in the aorta and lungs of CypD knockout mice.

127 results indicate that the Cys-203 residue of CypD is necessary for redox stress-induced activation of

128 Our data (1) point to a new role of CypD at the ER-mitochondria interface and (2) suggest th

129 To investigate the role of CypD in cell death, we created a CypD-deficient mouse.

130 Consistent with the reported role of CypD in mPTP activation, CypD null (CypD(-/-)) MEFs exhi

131 nuates loss of synapse, suggesting a role of CypD-dependent signaling in Abeta-induced alterations in

132 en new high-resolution crystal structures of CypD-inhibitor complexes were obtained to guide compound

133 uman endothelial cells, genetic targeting of CypD using siRNA or shRNA resulted in a constitutive inc

134 kout mice was significantly stronger than of CypD-deficient mice.

135 d human primary hepatocytes and treatment of CypD knockout mice with metformin improved both insulin

136 The fact that some tumors overexpress CypD suggests that this may be an additional mechanism o

137 reasing organelle contacts by overexpressing CypD enhanced insulin action in primary hepatocytes of d

138 Our study identifies the mitochondrial p53-CypD axis as an important contributor to oxidative stres

139 Intriguingly, a robust p53-CypD complex forms during brain ischemia/reperfusion inj

140 The responsible CypD residues for this activity were mapped by NMR to th

141 These findings suggest that selective CypD inhibition may represent a viable therapeutic strat

142 prevented by cotreatment with the selective CypD inhibitor, Debio 025 (alisporivir, DEB025, a nonimm

143 Downstream of SIRT1, CypD-deficient endothelial cells exhibited reduced phosp

144 Silencing or disruption of SPG7-CypD binding prevented Ca(2+)- and ROS-induced DeltaPsim

145 Notably, blockade of the F1F0 ATP synthase-CypD interaction by CypD ablation protected against diab

146 pD triggers enhancement of F1F0 ATP synthase-CypD interaction, which in turn leads to mPTP opening.

147 d synthesized a new mitochondrially targeted CypD inhibitor, JW47, using a quinolinium cation tethere

148 We conclude that CypD not only regulates the PTP, but also regulates the

149 nd loss-of-function experiments confirm that CypD has a limiting effect on cytochrome c release from

150 Our data indicate that CypD indeed interacts with Bcl2 as confirmed with co-imm

151 We report that CypD interacts with the VDAC1/Grp75/IP3R1 complex in car

152 Several reports have shown that CypD is overexpressed in various tumors, where it has an

153 apoptotic stimuli as the WT, suggesting that CypD is not a central component of cell death in respons

154 The CypD-deficient cortical mitochondria are resistant to Ab

155 in D inhibitor, cyclosporine A, disrupts the CypD-Bcl2 interaction.

156 A dehydrogenase, which was acetylated in the CypD(-/-) hearts.

157 ellular NAD(+)/NADH ratio and normalized the CypD-deficient phenotype.

158 drial permeabilization, independently of the CypD-regulated mPT, we coadministered the peroxynitrite

159 Thermodynamic profiles of the CypD/inhibitor interactions were determined by isotherma

160 Thus, the CypD-mediated mitochondrial permeability transition pore

161 ion of mitochondrial Ca(2+) overload via the CypD/VDAC1/Grp75/IP3R1 complex.

162 Therefore, CypD directs mitochondria-to-nuclei inflammatory gene ex

163 ntraperitoneal, 90 minutes prior to APAP) to CypD-deficient mice.

164 Genetic targeting of Hsp60 by siRNA triggers CypD-dependent mitochondrial permeability transition, ca

165 In vitro, CypD-deficient mitochondria showed an increased capacity

166 hat respond to metabolic demands and whether CypD regulates this dynamic.

167 whether there is one common pathway in which CypD and RIPK1 act in or whether separate RN pathways ex

168 s, blockade of ATP synthase interaction with CypD provides a promising new target for therapeutic int

169 mbinant adenovirus encoding C203S-CypD or WT CypD into CypD(-/-) mice via tail vein.

170 Ca(2+)-induced swelling as compared with WT CypD-reconstituted mice.