ライフサイエンスコーパス: SIRT3

1 ated with reduced levels of renal sirtuin 3 (SIRT3).

2 and high isozyme selectivity over SIRT1 and SIRT3.

3 HKL depend on activation of the deacetylase Sirt3.

4 that deacetylation depends on mitochondrial SIRT3.

5 ke and cell proliferation, are controlled by SIRT3.

6 tribute to the tumor-suppressive activity of SIRT3.

7 cellent selectivity for SIRT2 over SIRT1 and SIRT3.

8 vity of SOD2 is regulated by the deacetylase SIRT3.

9 stress response is under dual regulation by SIRT3.

10 ion through the NAD(+)-dependent deacetylase SIRT3.

11 sirt2, which is homologous to human sir2 and sirt3.

12 Our SIRT3-5 interaction network provides a framework for dis

13 Mitochondrial sirtuins, SIRT3-5, are NAD(+)-dependent deacylases and ADP-ribosyl

14 Although Sirtuin 3 (SIRT3), a mitochondrially enriched deacetylase and activ

15 ective effects by up-regulating the level of Sirt3, a member of Sirtuin family protein located in mit

16 are previous observations that expression of SIRT3, a nutrient stress sensor and regulator of mitocho

17 se mice, in which SIRT1 activity is low, and SIRT3 acetylation at Lys(57) inhibits its deacetylase ac

18 mitochondrial SIRT3 functions by inhibiting SIRT3 acetylation may offer a new therapeutic approach f

19 Furthermore, genetic and pharmacologic SIRT3 activation blunted NLRP3 activity in parallel with

20 SIRT3 activation could be a potential therapy for DOX-in

21 This effect might be mediated by SIRT3 activation, controlling mitochondrial reactive oxy

22 SIRT3 activity and expression transiently increased foll

23 this study, we examined whether the loss of Sirt3 activity increases vascular oxidative stress becau

24 Increased Sirt3 activity is associated with reduced acetylation of

25 e assessed by using immunohistochemistry for SIRT3 activity via acetylated MnSOD(K68) Murine AEC SIRT

26 did not lead to significant modifications in SIRT3 activity, the major mitochondrial lysine deacetyla

27 induce mitochondrial deacetylase sirtuin-3 (SIRT3) activity, disrupted mitochondrial structure, decr

28 Our study suggests that SIRT3 acts as a tumor suppressor in B cell malignancies,

29 There is controversy as to whether SIRT3 acts as an oncogene or a tumor suppressor, and her

30 Our data reveal that SirT3 acts to orchestrate two pathways, the antioxidant

31 We confirmed the SIRT-RELB-SIRT3 adaptation link to mitochondrial bioenergetics in

32 AICAR nor ALCAR treatment prevented death in Sirt3-/- AKI mice.

33 s by a process that requires skeletal muscle SIRT3-AMPK-GLUT4 signaling.

34 ND#115926) displayed increased activation of SIRT3 and AMP-activated protein kinase.

35 el with robust activation of skeletal muscle SIRT3 and AMP-activated protein kinase.

36 ctivity via acetylated MnSOD(K68) Murine AEC SIRT3 and cleaved caspase-9 (CC-9) expression were assay

37 sphorylation of PDP1 dissociates deacetylase SIRT3 and recruits acetyltransferase ACAT1 to PDC, resul

38 However, mice lacking both SIRT3 and SIRT5 (Sirt3(-/-)Sirt5(-/-) mice) exhibited si

39 These results suggest that SIRT3 and SIRT5 may be involved in regulating neuronal d

40 Surprisingly, the mitochondrial sirtuins Sirt3 and Sirt5 were resistant to inhibition by cysteine

41 ious human sirtuins, including SIRT1, SIRT2, SIRT3 and SIRT5.

42 vitro following matrix detachment, and both SIRT3 and SOD2 are necessary for colonization of the per

43 and DOX induced a dose-dependent decrease in SIRT3 and SOD2 expression in H9c2 cardiomyocytes.

44 ing mitochondria-targeted catalase prevented Sirt3 and SOD2 impairment and attenuated hypertension.

45 on was markedly increased in Sirt3-knockout (Sirt3(-/)(-)) and SOD2-depleted (SOD2(+/)(-)) mice in re

46 pressure and improved vasorelaxation both in Sirt3(-/-) and wild-type mice.

47 ion, including sirtuin 1 (SIRT1), sirtuin 3 (SIRT3), and Nrf-1.

48 showed increased expression of Pgc1alpha and Sirt3, and improved mitochondrial respiration, compared

49 letion from rod photoreceptors, mice lacking SIRT3, and mice lacking SIRT5 and tested multiple compon

50 ic bone turnover, is not reliant upon active SIRT3, and our results highlight the need to examine kno

51 of the SIRT2 acyl pocket to those of SIRT1, SIRT3, and SIRT6 reveals that the acyl pockets of SIRT1-

52 orms, silent information regulator (SIRT) 1, SIRT3, and SIRT6, play an essential role in the regulati

53 focus primarily on mammalian sirtuins SIRT1, SIRT3, and SIRT6, the three sirtuins for which the most

54 poptosis in wild-type mice were amplified in Sirt3(-/-) animals.

55 Here we demonstrate that Sirt1, Sirt2, and Sirt3 are expressed in enucleate platelets.

56 , the cytosolic Sirt2, and the mitochondrial Sirt3 are robust deacetylases, whereas the other sirtuin

57 creening of DLBCL patient samples identified SIRT3 as a putative therapeutic target, and validated an

58 Our data predicts SIRT3 as an important therapeutic target for DLBCL patie

59 eover, we identified mitochondrial ACAT1 and SIRT3 as the upstream acetyltransferase and deacetylase,

60 equire the mitochondrial protein deacetylase SIRT3 as they are abolished in SIRT3-deficient mice and

61 Our results suggest that overexpression of SIRT3 attenuates DOX-induced ROS production, and this ma

62 and metabolic conditions further inactivate Sirt3 because of increased NADH (nicotinamide adenine di

63 In healthy mitochondria, a pool of SIRT3 binds ATP synthase, but upon matrix pH reduction w

64 vers a fundamental role for sequestration of SIRT3 by ATP synthase in mitochondrial homeostasis.

65 chanism operates to induce its own inhibitor SIRT3 by PGC-1beta.

66 in 129SJ/wild-type and SIRT3-knockout mice (Sirt3(-/-) ) by using fibrosis scoring and lung collagen

67 sion of mitochondrial deacetylase sirtuin 3 (SIRT3) by androgen receptor (AR) and its coregulator ste

68 t that HKL is a pharmacological activator of Sirt3 capable of blocking, and even reversing, the cardi

69 Analysis of the most functionally cohesive Sirt3 co-expressed gene set revealed core metabolic path

70 We examined Sirtuin-3 (Sirt3) co-expressed gene sets extracted from either live

71 Here, we show that SIRT3 controls transformation of fibroblasts into myofib

72 ertension showing a 40% decrease in vascular Sirt3, coupled with Sirt3-dependent 3-fold increases in

73 mitochondrial metabolic homeostasis via CDK1-SIRT3-CPT2 cascade.

74 ollowing increased expression, mitochondrial SIRT3 deacetylase activates the rate-limiting tricarboxy

75 SIRT3 deacetylated and activated GSK3beta and thereby bl

76 lorie restriction, mitochondrial deacetylase Sirt3 deacetylates and activates IDH2, thereby regulatin

77 Sirtuin 3 (SIRT3) deacetylates and regulates many mitochondrial pro

78 l long-chain acyl-CoA dehydrogenase, a known SIRT3 deacetylation target; improved fatty acid beta-oxi

79 Overexpression of SIRT3 decreased proliferation and diminished the Warburg

80 observed in response to pressure overload or Sirt3 deficiency alone.

81 SIRT3 deficiency caused induction of TGF-beta1 expressio

82 using the mouse digit amputation model, that SIRT3 deficiency has no impact on the regenerative capac

83 These data suggest a novel role for SIRT3 deficiency in mediating AEC mtDNA damage, apoptosi

84 We reasoned that SIRT3 deficiency occurs in fibrotic lungs and thereby au

85 SIRT3 deficiency promotes lung fibrosis by augmenting al

86 Importantly, SIRT3 deficiency results in a defect in cellular iron ho

87 Regeneration occurs in SIRT3 deficient mice in spite of the reduced oxidative m

88 and diminished the Warburg-like phenotype in SIRT3-deficient cell lines, and this effect is largely d

89 y and mutagenesis analyses indicated that in SIRT3-deficient cells OPA1 was acetylated at lysine 926

90 -lowering effect of nitrite was abolished in SIRT3-deficient human skeletal muscle cells, and in SIRT

91 n deacetylase SIRT3 as they are abolished in SIRT3-deficient mice and wild type mice in which SIRT3 i

92 Moreover, Sirt3-deficient mice given cisplatin experienced more se

93 40% decrease in vascular Sirt3, coupled with Sirt3-dependent 3-fold increases in SOD2 acetylation, NF

94 data support the hypothesis that IR triggers SIRT3-dependent deacetylation of ceramide synthases and

95 to cellular detachment, which is followed by SIRT3-dependent increases in SOD2 mRNA during sustained

96 n and differentiation to myofibroblasts in a Sirt3-dependent manner.

97 cits in hippocampal synaptic plasticity in a SIRT3-dependent manner.

98 rts NAFLD by inducing a sirtuin (SIRT)1- and SIRT3-dependent mitochondrial unfolded protein response,

99 or, YC8-02, which phenocopied the effects of SIRT3 depletion and killed DLBCL cells.

100 Mechanistically, SIRT3 depletion impaired glutamine flux to the TCA cycle

101 We suggest that Sirt3 depletion in hypertension promotes endothelial dys

102 Global Sirt3 depletion in Sirt3(-/-) mice results in oxidative

103 Sirt3 depletion increased SOD2 acetylation, elevated mit

104 The clinical relevance of Sirt3 depletion was confirmed in arterioles from human m

105 Sirtuin 3 (SIRT3) detoxifies mitochondrial reactive oxygen species,

106 etic diets may be mediated, in part, through SIRT3-directed blunting of NLRP3 inflammasome assembly a

107 in the mitochondria of SIRT3-null mice, and SIRT3 directly deacetylates the ceramide synthases in a

108 nt loss of mitochondrial membrane potential, SIRT3 dissociates.

109 re assayed by immunoblotting with or without SIRT3 enforced expression or silencing.

110 al protein acetylation, including MnSOD(K68) SIRT3 enforced expression reduced oxidant-induced AEC OG

111 show, for the first time, that mice lacking SIRT3 exhibit increased insulin resistance due to defect

112 Mice deficient in SIRT3 exhibited severe osteopenia owing to increased num

113 nt agent acetyl-l-carnitine (ALCAR) restored SIRT3 expression and activity, improved renal function,

114 r SIRT1 guides RELB to differentially induce SIRT3 expression and also increases mitochondrial biogen

115 Our data suggest that diminished Sirt3 expression and redox inactivation of Sirt3 lead to

116 T3 promoter, and depletion of SRC-2 enhanced SIRT3 expression and simultaneously reduced acetylated A

117 metastasis, suppression of SRC-2 reactivated SIRT3 expression and was sufficient to abolish prostate

118 We hypothesized that reduced Sirt3 expression contributes to vascular dysfunction in

119 SIRT3 expression from RANKL induction depended on the tr

120 While manipulation of SIRT3 expression has few deleterious effects on cancer c

121 ependent hypertension; conversely, increased Sirt3 expression in Sirt3OX mice prevents these deleteri

122 support a therapeutic potential of targeting Sirt3 expression in vascular dysfunction and hypertensio

123 Indeed, SIRT3 expression is negatively correlated with TfR1 expr

124 and suggests that blocking SRC-2 to enhance SIRT3 expression may be therapeutically valuable.

125 hat HKL is present in mitochondria, enhances Sirt3 expression nearly twofold and suggest that HKL may

126 In vivo studies using gain and loss of SIRT3 expression showed that SIRT3 promotes growth of AT

127 nistration of DOX to mice suppressed cardiac SIRT3 expression, and DOX induced a dose-dependent decre

128 c wound macrophages and, in turn, diminishes SIRT3 expression, thereby promoting inflammation.

129 test the therapeutic potential of targeting Sirt3 expression, we developed new transgenic mice with

130 reatic tumors, which correlates with reduced SIRT3 expression.

131 ated an inverse relationship between ATM and SIRT3 expression.

132 ependent on mitochondrial lysine deacetylase SIRT3 for proliferation, survival, self-renewal, and tum

133 vity, and differentiation, the importance of SIRT3 for regeneration after bone injury has never been

134 Lastly, depletion of SIRT3 from malignant B cell lines resulted in greater su

135 ism through IRP1 regulation and suggest that SIRT3 functions as a tumor suppressor, in part, by modul

136 Improving mitochondrial SIRT3 functions by inhibiting SIRT3 acetylation may offe

137 Overexpression of Sirt3 further prevented LPS-induced pericyte loss and va

138 Importantly, Sirt3 gene ablation reduced the brain injury after IR.

139 uclear respiratory factor 2 (Nrf2)-dependent Sirt3 gene transcription.

140 ofiles are tightly regulated and the loss of SIRT3 has deleterious effects on bone volume in vivo and

141 LPS significantly reduced the expression of SIRT3, HIF-2alpha and Notch3 in the lung.

142 Mice were exposed to LPS, expression of Sirt3, HIF-2alpha, Notch3 and angiopoietins/Tie-2, peric

143 together, these findings indicate that NAMPT/SIRT3/IDH2 pathway inhibition enhances the therapeutic e

144 Sirt3 impairment reduces the activity of a key mitochond

145 But a physiological role of SIRT3 in bone metabolism is not known.

146 Our data uncover a novel role of SIRT3 in cellular iron metabolism through IRP1 regulatio

147 nd CerS6, but not CerS4, are associated with SIRT3 in cerebral mitochondria.

148 These results show that the absence of SIRT3 in HFD-fed mice causes profound impairments in ins

149 In addition, we found that FABP4 regulates SIRT3 in human blood monocytes, and inhibition of FABP4

150 e, a short hairpin RNA-mediated knockdown of SIRT3 in human melanoma cells resulted in (i) a decrease

151 This study investigated the involvement of SIRT3 in LPS-induced pericyte loss and microvascular dys

152 supporting the pro-proliferative function of SIRT3 in melanoma.

153 lps orchestrate nuclear oxidant defenses and Sirt3 in mice led to a clear age-related loss of SNc dop

154 iosynthesis and suggest an important role of SIRT3 in mitochondrial dysfunction and brain injury afte

155 vel context-specific, pro-metastatic role of SIRT3 in ovarian cancer.

156 Our study demonstrates the importance of SIRT3 in preserving vascular integrity by targeting peri

157 highlight the need to examine known roles of SIRT3 in the context of injury.

158 significance of the mitochondrial sirtuin 3 (SIRT3) in melanoma.

159 Overexpression of wild-type SIRT3 increased cardiolipin levels and rescued mitochond

160 e mitochondrial-enriched sirtuin deacetylase SIRT3 increased NLRP3 inflammasome activation in associa

161 Indeed, genetic deletion of Sirt3 increased oxidative stress and decreased the membr

162 ctor-1alpha pathway, suggesting that loss of SIRT3 increases proliferation via ROS-dependent but hypo

163 n receptor-related receptor alpha), and that SIRT3 inhibited the differentiation by interfering with

164 tly, combination of CFZ with either NAMPT or SIRT3 inhibitors impaired IDH2 activity and increased MM

165 In addition, SIRT3 inhibits glycolytic capacity in anchorage-independ

166 these studies highlight a novel mechanism of SIRT3 involvement in modulating mitochondrial ceramide b

167 e consistent with other studies that suggest Sirt3 is a key metabolic regulator and has distinct func

168 Here we show that SIRT3 is a key regulatory molecule to maintain bone home

169 Our results suggest that a mitochondrial SIRT3 is an intrinsic inhibitor for RANKL-mediated osteo

170 Here, we found that SIRT3 is essential for normal healing and regulates infl

171 SIRT3 is hyperacetylated in aged and obese mice, in whic

172 Together, our results indicate that SIRT3 is protective against AKI and suggest that enhanci

173 rapid deacetylation of matrix proteins, and SIRT3 is required for recovery of membrane potential.

174 Here we show that SIRT3 is reversibly acetylated in the mitochondria and u

175 3-deficient mice and wild type mice in which SIRT3 is selectively depleted from hippocampal neurons.

176 primary and immortalized human melanocytes, SIRT3 is significantly overexpressed in multiple human m

177 oying human tissue microarray, we found that SIRT3 is significantly upregulated in clinical melanoma

178 SIRT3 is thus a metabolic non-oncogene addiction and the

179 n deacetylating and altering the function of SIRT3 is unknown.

180 Sirtuin-3 (SIRT3) is a class III lysine deacetylase that is localiz

181 Sirtuin-3 (Sirt3) is a mitochondrial deacetylase that could mediate

182 The mitochondrial sirtuin 3 (SIRT3) is involved in suppressing the onset of multiple

183 The mitochondrial deacetylase sirtuin 3 (SIRT3) is thought to be one of the main contributors to

184 were not observed with an acetylation-mimic SIRT3-K57Q mutant.

185 ression of SIRT3 or an acetylation-defective SIRT3-K57R mutant in diet-induced obese mice decreased a

186 In SIRT3 knock-out bone marrow-derived macrophages, NLRP3 a

187 nse to nutrient deprivation in wild-type and SIRT3 knock-out mice.

188 he inflammasome in wild-type mice but not in SIRT3 knock-out mice.

189 Finally, we found that SIRT3 knockdown significantly inhibited tumorigenesis in

190 Permeabilized muscle fibers from HFD-fed SIRT3 knockout (KO) mice showed that tricarboxylic acid

191 We found that Sirt3 knockout (KO) mice with age develop tissue fibrosi

192 SIRT3 knockout attenuated B cell lymphomagenesis in VavP

193 eficient human skeletal muscle cells, and in SIRT3 knockout mice fed a high-fat diet, as well.

194 S AND Hypertension was markedly increased in Sirt3-knockout (Sirt3(-/)(-)) and SOD2-depleted (SOD2(+/

195 xposure was evaluated in 129SJ/wild-type and SIRT3-knockout mice (Sirt3(-/-) ) by using fibrosis scor

196 e potential of SNc dopaminergic neurons from Sirt3 knockouts.

197 lated lysine peptides measured in DKO versus Sirt3 KO hearts were strongly correlated.

198 chondria is decreased in muscle from HFD-fed SIRT3 KO mice, suggesting decreased HKII activity.

199 macrophage cytokines, including IL-1beta, in SIRT3 KO mice.

200 Insulin action was not impaired in the lean SIRT3 KO mice.

201 duces ROS synthesis in wild type, but not in Sirt3-KO cells.

202 d Sirt3 expression and redox inactivation of Sirt3 lead to SOD2 inactivation and contributes to the p

203 cardiovascular disease risk factors diminish Sirt3 level.

204 l otoprotective small molecule via elevating Sirt3 levels and Sirt3 may be of therapeutic value in ha

205 ng oxidative stress, whereas Sirt6 maintains Sirt3 levels by up-regulating nuclear respiratory factor

206 and that, in response to prolonged fasting, SIRT3 levels modulate mitochondrial protein folding.

207 in SOD2 acetylation and 1.4-fold decrease in Sirt3 levels, whereas SOD2 expression was not affected.

208 SIRT3 loss increases reactive oxygen species production,

209 er, these studies demonstrate that Sirt6 and Sirt3 maintain each other's activity and protect the hea

210 mall molecule via elevating Sirt3 levels and Sirt3 may be of therapeutic value in hair cell protectio

211 These SIRT3-mediated beneficial effects were not observed with

212 brain ischemia/reperfusion (IR) showed that SIRT3-mediated deacetylation of ceramide synthases incre

213 mmasome components but, rather, occurred via SIRT3-mediated deacetylation of mitochondrial SOD2, lead

214 In fasted liver, SIRT3-mediated increases in substrate flux depend on oxi

215 late the NLRP3 inflammasome, in part through SIRT3-mediated mitochondrial homeostatic control.

216 attached conditions, SIRT3 upregulation and SIRT3-mediated oxidant scavenging are required for anoik

217 Sirtuin 3 (SIRT3) mediates histone protein post-translational modif

218 Global Sirt3 depletion in Sirt3(-/-) mice results in oxidative stress due to hyper

219 duced blood pressure in wild-type but not in Sirt3(-/-) mice, whereas an SOD2 mimetic, (2-[2,2,6,6-te

220 Osteoclast precursors from Sirt3-/- mice underwent increased osteoclastogenesis in

221 r injury in WT animals, but had no effect in Sirt3-/- mice.

222 SIRT3 null cells contain high levels of iron and lose ir

223 Moreover, SIRT3 null mice exhibit higher levels of iron and TfR1 e

224 6 are hyperacetylated in the mitochondria of SIRT3-null mice, and SIRT3 directly deacetylates the cer

225 SIRT3-null mouse embryonic fibroblasts produced signific

226 restingly, the negative regulatory effect of SIRT3 on NLRP3 was not due to transcriptional control or

227 Adenovirus-mediated expression of SIRT3 or an acetylation-defective SIRT3-K57R mutant in d

228 We also found that siRNA knockdown of SIRT3 or SOD2 increased NLRP3 supercomplex formation and

229 ppearing retinal morphology in hyperglycemic Sirt3(-/-) or Sirt5(-/-) mice.

230 Moreover, Sirt3-/- osteoclast precursors reduced AMP-activated pro

231 liver, kidney, and lungs but not whole-body SIRT3-overexpressing mice.

232 SIRT3 overexpression decreases TfR1 expression by inhibi

233 ped new transgenic mice with global Sirt3OX (Sirt3 overexpression), which protects from endothelial d

234 r in B cell malignancies, and activating the SIRT3 pathway might represent a novel therapeutic approa

235 al homeostasis is regulated by CDK1-mediated SIRT3 phosphorylation, which in turn deacetylates and di

236 Mechanistic studies showed that Sirt3 preserves Sirt6 levels by reducing oxidative stres

237 rpose of this study was to determine whether SIRT3 prevents DOX-induced mitochondrial ROS production.

238 Mechanistically, SIRT3 prevents mitochondrial superoxide surges in detach

239 26 probes that targeted different regions of Sirt3 primary transcript.

240 ng from 100-1000 genes) associated with each Sirt3 probe were evaluated using the previously develope

241 he LPv approach can distinguish high quality Sirt3 probes.

242 nversely, forced exogenous overexpression of SIRT3 promoted an increase in proliferative potential of

243 x by recruiting histone deacetylase 2 to the SIRT3 promoter, and depletion of SRC-2 enhanced SIRT3 ex

244 ain and loss of SIRT3 expression showed that SIRT3 promotes growth of ATM CRISPR knockout DLBCL xenog

245 In summary, these data indicated that SIRT3 promotes mitochondrial function not only by regula

246 udies suggest that an age-related decline in Sirt3 protective function is a major factor underlying i

247 This suggests that SIRT3 protects against dietary insulin resistance by fac

248 r dysfunction in hypertension, but increased Sirt3 protects vascular function and decreases hypertens

249 Asbestos and H2O2 diminished AEC SIRT3 protein expression and increased mitochondrial pro

250 ymphoma patient samples, we found that lower SIRT3 protein expression was associated with worse overa

251 Further, SIRT3 protein expression was reduced in chronic lymphocy

252 SIRT3 rapidly increases SOD2 activity as an early adapta

253 Conversely, overexpression of Sirt3 reduced Ang-2 expression and increased Ang-1/Tie-2

254 ther, these data demonstrate that NAD(+) and SIRT3 regulate microtubule polymerization and the effica

255 uclear and mitochondrial sirtuins, Sirt6 and Sirt3, regulate each other's activity and protect the he

256 nuclear Sirt, Sirt6, and mitochondrial Sirt, Sirt3, regulate each other's activity and protect the he

257 Using mass spectrometry, we identified SIRT3-regulated lysine residues in LRP130 that generated

258 Here, we report that mitochondrial SIRT3 regulates cellular iron metabolism by modulating I

259 Herein, we report that SIRT3 regulates mitochondrial ceramide biosynthesis via

260 findings reveal an unexpected mechanism for SIRT3 regulation via SIRT1-mediated deacetylation.

261 engineered cells, indicate that pH-dependent SIRT3 release requires H135 in the ATP5O subunit of ATP

262 ctional studies demonstrated that absence of SIRT3 rescued the IR-induced blockade of the electron tr

263 tured human tubular cells, cisplatin reduced SIRT3, resulting in mitochondrial fragmentation, while r

264 m mitochondrial fragmentation and decline of Sirt3, resulting otherwise from HF-HS diet feeding.

265 Investigation of the SIRT3 role in mitochondrial response to brain ischemia/r

266 Sirt3 silencing experiments confirmed that Sirt3-ROS signaling axis mediated hair cell protection a

267 II-induced hypertension was associated with Sirt3 S-glutathionylation, acetylation of vascular SOD2,

268 hydrogen peroxide scavenger ebselen, reduced Sirt3 S-glutathionylation, diminished SOD2 acetylation,

269 unction and metabolic fitness likely through Sirt3 signaling.

270 ls with NAT1 and either SIRT 1 or 2, but not SIRT3, significantly decreased NAT1 acetylation.

271 Sirt3 silencing experiments confirmed that Sirt3-ROS sig

272 lation, mtDNA damage, and apoptosis, whereas SIRT3 silencing promoted these effects.

273 However, mice lacking both SIRT3 and SIRT5 (Sirt3(-/-)Sirt5(-/-) mice) exhibited significant evidenc

274 ne deacetylase sirtuin family (SIRT1, SIRT2, SIRT3, SIRT5 and SIRT6) using both recombinant enzymes a

275 ibit the deacylase activity of Sirt1, Sirt2, Sirt3, Sirt5, and Sirt6.

276 RATIONALE: Clinical studies have shown that Sirt3 (Sirtuin 3) expression declines by 40% by 65 years

277 The mitochondrial deacetylase Sirt3 (Sirtuin 3) is critical in the regulation of metab

278 SIRT3 (sirtuin 3) is the major deacetylase within the mi

279 es in CrAT (carnitine acetyltransferase) and Sirt3 (sirtuin 3)-enzymes that oppose Kac by buffering t

280 We demonstrate that Hsp10 is a functional SIRT3 substrate and that, in response to prolonged fasti

281 ed with reduced acetylation of mitochondrial Sirt3 substrates, MnSOD and oligomycin-sensitivity confe

282 he unknown cellular mechanisms controlled by Sirt3, that have previously been considered solely as a

283 Sirtuin 3 (SIRT3), the primary mitochondrial deacetylase, has been

284 rly twofold and suggest that HKL may bind to Sirt3 to further increase its activity.

285 ctive against AKI and suggest that enhancing SIRT3 to improve mitochondrial dynamics has potential as

286 These data reveal a new role of SIRT3 to negatively regulate aging-associated tissue fib

287 Intriguingly, knockout of Sirt3 upregulated Ang-2, but downregulated Tie-2 and HIF

288 ects on cancer cells in attached conditions, SIRT3 upregulation and SIRT3-mediated oxidant scavenging

289 and 8 with 6.8- and 5.3-fold selectivity for SIRT3 versus SIRT1 and SIRT2, respectively.

290 The mitochondrial deacetylase SIRT3 was capable of deacetylating OPA1 and elevating it

291 Under prediabetic conditions, SIRT3 was decreased in wound macrophages and resulted in

292 Increased activity of SIRT3 was evidenced by normalization of the increased ac

293 cts were absent when a deacetylase-deficient SIRT3 was expressed in H9c2 cells.

294 ssion of SRC-2 with concomitant reduction of SIRT3 was found to be a genetic hallmark enriched in pro

295 We found that expression of both Sirt6 and Sirt3 was reduced in cardiomyocytes treated with palmita

296 Deletion of Pgc1alpha or Sirt3, which are key regulators of OXPHOS, abrogated Tre

297 ogenic effects of nutrients were reversed by SIRT3, which deacetylates lys(101) acetylation.

298 tylation of ACO2 was reversibly regulated by SIRT3, which was predominantly repressed in many tumors

299 l acetylation state, via genetic deletion of SIRT3, will amplify the deleterious effects of a high-fa

300 hondrial fragmentation, while restoration of SIRT3 with AICAR and ALCAR improved cisplatin-induced mi