ライフサイエンスコーパス: mPTP

1 mPTP opening decreases the mitochondrial membrane potent

2 mPTP opening has been implicated as a final cell death p

3 mPTP-dependent alkalinization occurred in procoagulant p

4 mPTP-induced depolarisation under succinate subsequently

5 A mPTP inhibitor (TRO-19622) or a specific mitochondria RO

6 fects were negated by the addition of ATR--a mPTP opener--and mimicked by injection of NIM811--a mPTP

7 ener--and mimicked by injection of NIM811--a mPTP opening inhibitor.

8 mplex I-driven respiration was reduced after mPTP opening but sustained in the presence of complex II

9 e whether mutation of C203S-CypD would alter mPTP in vivo, we injected a recombinant adenovirus encod

10 MKII inhibitory protein or cyclosporin A, an mPTP antagonist with clinical efficacy in ischaemia repe

11 ethyl-4-isoleucine cyclosporine (NIM811), an mPTP inhibitor, were administered separately in selected

12 Accordingly, cyclophilin-D and mPTP were increased in heterozygous hearts, but genetic

13 a-AR stimulation that links CaMKII, Drp1 and mPTP to bridge cytosolic stress signal with mitochondria

14 Bcl-2 family proteins and mPTP-regulatory elements, such as adenine nucleotide tra

15 The activity of the cinnamic anilide mPTP inhibitors turned out to be additive with that of C

16 s increased cyclophilin-D levels, as well as mPTP activation upon oxidative stress.

17 CypD(-/-) MEFs prior to H(2)O(2) attenuated mPTP opening.

18 ither iPLA2gamma or lipoxygenases attenuated mPTP opening in failing hearts.

19 y preventing mitochondrial Ca(2+) influx, by mPTP inhibitor cyclosporine A, sanglifehrin, and in cycl

20 ets, integrin alphaIIbbeta3 epitope changes, mPTP formation, PS exposure, and platelet rounding were

21 ance consistent with this c-subunit channel (mPTP) in brain-derived submitochondrial vesicles (SMVs)

22 mbrane function, but its role in controlling mPTP activity remains obscure.

23 eine 203 of cyclophilin D (CypD), a critical mPTP mediator, undergoes protein S-nitrosylation (SNO).

24 LA2gamma loss of function through decreasing mPTP opening, diminishing production of proinflammatory

25 which interacts with cyclophilin D to delay mPTP opening, were necessary to increase the Ca2+ uptake

26 therefore understanding conditions dictating mPTP opening is crucial for developing targeted therapie

27 e ATP synthase F1, providing a mechanism for mPTP opening.

28 Increasing the ROS threshold for mPTP induction enhances the resistance of cardiomyocytes

29 t Bax-driven fusion lowers the threshold for mPTP opening and necrosis.

30 To investigate the role of cysteine 203 in mPTP activation, we mutated cysteine 203 of CypD to a se

31 NO, suggesting a crucial role for Cys-203 in mPTP activation.

32 Consistent with the reported role of CypD in mPTP activation, CypD null (CypD(-/-)) MEFs exhibited si

33 cyclophilin-D levels leading to reduction in mPTP activation.

34 calcium stimuli become sufficient to induce mPTP opening in PINK1-deficient cells.

35 toyl-CoA markedly accelerated Ca(2+)-induced mPTP opening in liver mitochondria from wild-type mice.

36 mice demonstrated attenuated Ca(2+)-induced mPTP opening that could be rapidly restored by the addit

37 he functional consequences of Ca(2+)-induced mPTP opening were assessed by Ca(2+) retention capacity,

38 ive animals, rotenone administration induced mPTP formation, ROS generation, and NLRP3 inflammasome a

39 CoA-mediated augmentation of calcium-induced mPTP opening.

40 oA-mediated amplification of calcium-induced mPTP opening.

41 ablation protected against diabetes-induced mPTP opening, ATP synthesis deficits, oxidative stress,

42 tant to Ca(2+)/t-butyl hydroperoxide-induced mPTP opening in comparison with wild-type littermates.

43 Drp1 activity blocks CaMKII- or ISO-induced mPTP opening and myocyte death in vitro and rescues hear

44 mPTP opening, attenuates isoflurane-induced mPTP opening, caspase 3 activation, and impairment of le

45 These compounds can inhibit mPTP opening in response to several stimuli including ca

46 of cyclosporine A being required to inhibit mPTP opening.

47 Inhibiting mPTP opening during the preconditioning phase with cyclo

48 kedly more potent than (S)-BEL in inhibiting mPTP opening in mitochondria from wild-type liver in com

49 in the absence of BSA, induced long-lasting mPTP opening, causing matrix depolarization.

50 CypD(-/-)) MEFs exhibited significantly less mPTP opening.

51 w insights into CypD-dependent mitochondrial mPTP and signaling on mitochondrial trafficking in axons

52 ated iPoC conferred protection by modulating mPTP.

53 oenergetics and lipidomic flux in modulating mPTP opening promoting the activation of necrotic and ne

54 anisms responsible for modulating myocardial mPTP opening remain unclear.

55 rome P450 epoxygenases opened the myocardial mPTP in human heart mitochondria.

56 grin beta3 cleavage and inactivation but not mPTP formation or PS exposure, indicating that integrin

57 additional tool to aid the search for novel mPTP modulators and to help understand its molecular nat

58 ly screen large compound libraries for novel mPTP modulators, a method was exploited to cryopreserve

59 esulting in protection against activation of mPTP and subsequent cell death responses.

60 ssary for redox stress-induced activation of mPTP.

61 Notably, blockade of mPTP by genetic deletion of CypD suppresses Abeta-mediat

62 Moreover, cyclosporine A, a blocker of mPTP opening, attenuates isoflurane-induced mPTP opening

63 state on the probability and consequences of mPTP opening.

64 ISO) persistently increases the frequency of mPTP openings followed by mitochondrial damage and cardi

65 Altogether, the inhibition of mPTP and the increase in mitochondrial biogenesis may ac

66 Furthermore, inhibition of mPTP opening by cyclosporin A partially prevented Cyto C

67 entified ER-000444793, a potent inhibitor of mPTP opening.

68 a2+ dynamics, we examined relative levels of mPTP components in synaptic versus nonsynaptic mitochond

69 f IPoC was associated with the modulation of mPTP opening.

70 rated that metformin inhibits the opening of mPTP and induces mitochondrial biogenesis.

71 inally, isoflurane may induce the opening of mPTP via increasing levels of reactive oxygen species.

72 ATR) and NIM811, which modify the opening of mPTP, were administered in selected groups.

73 an unexpected role of HAX-1 in regulation of mPTP and cardiomyocyte survival.

74 downstream products as potent regulators of mPTP opening, and demonstrate the integrated roles of mi

75 holipid scrambling with an assistant role of mPTP formation.

76 residue (C203S) and determined its effect on mPTP opening.

77 ive oxygen species (ROS) levels, and an open mPTP.

78 ) may be molecularly related to pathological mPTP, but are likely to be normal physiological manifest

79 pore size is much smaller than for permanent mPTP, as neither Rhod-2 nor calcein (600 Da) were lost.

80 Furthermore, platelet mPTP formation resulted in a decreased ability to recrui

81 cate that, in strongly stimulated platelets, mPTP formation initiates the calpain-dependent cleavage

82 cular identity of the mitochondrial PT pore (mPTP) was previously unknown.

83 mitochondrial permeability transition pore (mPTP) and contribute to the production of oxidized fatty

84 mitochondrial permeability transition pore (mPTP) and the new phenomenon, superoxide flashes, and RO

85 mitochondrial permeability transition pore (mPTP) as a key end effector of ischemic/pharmacological

86 mitochondrial permeability transition pore (mPTP) based on the findings that cyclosporin A (CsA), a

87 mitochondrial permeability transition pore (mPTP) drives maturation of mitochondrial structure and f

88 mitochondrial permeability transition pore (mPTP) formation, agonist-induced phosphatidylserine expo

89 Mitochondrial permeability transition pore (mPTP) formation, which is essential for the formation of

90 mitochondrial permeability transition pore (mPTP) in Abeta-impaired axonal mitochondrial trafficking

91 mitochondrial permeability transition pore (mPTP) inhibitors.

92 Mitochondrial permeability transition pore (mPTP) is involved in cardiac dysfunction during chronic

93 mitochondrial permeability transition pore (mPTP) may limit mitochondrial calcium load and mediate m

94 mitochondrial permeability transition pore (mPTP) opener, and N-methyl-4-isoleucine cyclosporine (NI

95 mitochondrial permeability transition pore (mPTP) opening and dissipation of the mitochondrial inner

96 mitochondrial permeability transition pore (mPTP) opening in brain mitochondria of diabetic mice, wh

97 mitochondrial permeability transition pore (mPTP) opening is a key pathophysiological event in cell

98 mitochondrial permeability transition pore (mPTP) opening plays a critical role in mediating cell de

99 mitochondrial permeability transition pore (mPTP) openings damage mitochondria, but transient mPTP o

100 mitochondrial permeability transition pore (mPTP) or the inner membrane anion channel (IMAC), respec

101 mitochondrial permeability transition pore (mPTP) such that physiological calcium stimuli become suf

102 mitochondrial permeability transition pore (mPTP) than nonsynaptic mitochondria.

103 mitochondrial permeability transition pore (mPTP) within the c-subunit of the ATP synthase.

104 mitochondrial permeability transition pore (mPTP), increase in levels of reactive oxygen species, re

105 mitochondrial permeability transition pore (mPTP), precipitating mitochondrial dysfunction and cessa

106 mitochondrial permeability transition pore (mPTP), resulting in disruption of mitochondria membrane

107 mitochondrial permeability transition pore (mPTP).

108 mitochondrial permeability transition pore (mPTP).

109 mitochondrial permeability transition pore (mPTP).

110 mitochondrial permeability transition pore (mPTP).

111 mitochondrial permeability transition pore (mPTP).

112 mitochondrial permeability transition pore (mPTP).

113 long-lasting permeability transition pores (mPTP) causes respiratory uncoupling, mitochondrial injur

114 mitochondrial permeability transition pores (mPTP).

115 ia through inhibition of fission potentiates mPTP opening in the absence of Bax/Bak or Mfn2, indicati

116 of these interactions to control and prevent mPTP induction when appropriate will enable us to decrea

117 mia reperfusion injury, equivalently prevent mPTP opening, DeltaPsim deterioration and diminish mitoc

118 Here we show that CaMKII promotes mPTP opening and myocardial death by increasing MCU curr

119 cally channels AA into toxic HETEs promoting mPTP opening, which induces necrosis/apoptosis leading t

120 cannot support MOMP and apoptosis, restores mPTP opening and necrosis, implicating distinct mechanis

121 3+/-3.1% with SfA; P<0.001), suggesting that mPTP opening during the preconditioning phase is require

122 The mPTP has been recently implicated in ROS generation via

123 functions to enhance ROS production and the mPTP and NO trigger apoptosis; thus, the mPTP is a targe

124 While it has long been clear the mPTP is a druggable target, current agents are limited b

125 -subunit leak channel is a candidate for the mPTP.

126 their strong dependence on IMAC and not the mPTP in this acute model of OS.

127 his series, able to attenuate opening of the mPTP and limit reperfusion injury in a rabbit model of a

128 Putative components of the mPTP are expressed in mouse LGN, including the voltage-d

129 activated the Ca(2+)-induced opening of the mPTP in failing human myocardium, and the highly selecti

130 Manipulation of the mPTP markedly attenuated the early preapoptotic producti

131 gation) and the structural components of the mPTP pore, inducing pore opening.

132 Pharmacologic and genetic closing of the mPTP yielded maturation of mitochondrial structure and f

133 as an important mechanistic component of the mPTP, define its downstream products as potent regulator

134 cyclophilin D, an essential regulator of the mPTP, exhibited delayed progression to heart failure and

135 s considered to be the core component of the mPTP, is not affected by the loss of PPIase activity.

136 ce, suggesting substantial activation of the mPTP.

137 at ER-000444793 acted as an inhibitor of the mPTP.

138 d a novel, CypD-independent inhibitor of the mPTP.

139 strate in adult mouse brain neurons that the mPTP functions to enhance ROS production and the mPTP an

140 the mPTP and NO trigger apoptosis; thus, the mPTP is a target for neuroprotection in vivo.

141 target(s) that act at or in proximity to the mPTP.

142 euron apoptosis as are mice treated with the mPTP inhibitors TRO-19622 (cholest-4-en-3-one oxime) and

143 ase-CypD interaction, which in turn leads to mPTP opening.

144 y which chronic beta-AR stimulation leads to mPTP openings is elusive.

145 electron transfer sensitised mitochondria to mPTP opening.

146 omplex III did not sensitise mitochondria to mPTP opening.

147 bsence of Bax/Bak renders cells resistant to mPTP opening and necrosis, effects confirmed in isolated

148 3S-CypD reconstituted MEFs were resistant to mPTP opening in the presence or absence of GSNO, suggest

149 mediated by distinct pathways subsequent to mPTP formation.

150 However, low conductance and transient mPTP openings (tPTP) might limit mitochondrial Ca(2+) lo

151 could be explained by asynchronous transient mPTP openings allowing individual mitochondria to depola

152 openings damage mitochondria, but transient mPTP openings protect against chronic cardiac stress.

153 ced CsA-sensitive, low-conductance transient mPTP opening (represented by a 28+/-3% reduction in mito

154 mitochondrial uncoupling requires transient mPTP opening and ROS.

155 We hypothesize that transient mPTP opening and ROS mediate the protection associated w

156 Our results show that transient mPTP openings allow cardiac mitochondria to defend thems

157 We found that transient mPTP openings also stimulated reactive oxygen species pr

158 al free [Ca(2+)] increase to >10 muM, unless mPTP openings were inhibited.

159 0-fold slower than matrix Ca(2+) release via mPTP, only a tiny fraction of mitochondria (<1%) are dep

160 of CyPD and VDAC oligomers, consistent with mPTP formation.