ライフサイエンスコーパス: alpha(1) antitrypsin

1 inactivation by alpha1-proteinase inhibitor (alpha1-antitrypsin).

2 emphysema caused by mutations in the serpin alpha1-antitrypsin.

3 ned significant amounts of human albumin and alpha1-antitrypsin.

4 fter its fragmentation in cells expressing Z-alpha1-antitrypsin.

5 bsence of polarity, and reduced secretion of alpha1-antitrypsin.

6 iver disease associated with the Z allele of alpha1-antitrypsin.

7 albumin, transferrin, alpha-fetoprotein, and alpha1-antitrypsin.

8 used by reduced level or loss of function of alpha1-antitrypsin.

9 -14, and cathepsin B and increased levels of alpha1-antitrypsin.

10 of repopulating liver cells expressing human alpha1-antitrypsin.

11 hepsins-K, -L, and -S) and the inhibition of alpha1-antitrypsin.

12 , and -S and the ability of IL-13 to inhibit alpha1-antitrypsin.

13 and 2300-fold higher than that of wild-type alpha1-antitrypsin.

14 ut compromising the inhibitory activity of Z alpha1-antitrypsin.

15 a loss of anti-inflammatory signalling by M alpha1-antitrypsin.

16 two GVHD severity markers, calprotectin and alpha1-antitrypsin.

17 , and this could be inhibited by addition of alpha1-antitrypsin.

18 nation and proteasomal degradation of mutant alpha1-antitrypsin.

19 h region and in beta-strand 1C compared with alpha(1)-antitrypsin.

20 oserpin while no such movement is evident in alpha(1)-antitrypsin.

21 cognizes the pathological polymers formed by alpha(1)-antitrypsin.

22 d secretion when compared to the wild-type M alpha(1)-antitrypsin.

23 diate their effects on the shutter region of alpha(1)-antitrypsin.

24 cy of the key anti-elastase within the lung: alpha(1)-antitrypsin.

25 e immune response and is homologous to human alpha(1)-antitrypsin.

26 heet in heparin-complexed antithrombin or in alpha(1)-antitrypsin.

27 rences between the pathogenic Z and normal M alpha(1)-antitrypsin.

28 be partially inserted into beta-sheet A in Z alpha(1)-antitrypsin.

29 (FLEAIG) that selectively and stably bound Z alpha(1)-antitrypsin.

30 the major target of inhibition of the serpin alpha(1)-antitrypsin.

31 it remains stable at approximately 3.5 A in alpha(1)-antitrypsin.

32 misfolded protein, null Hong Kong variant of alpha(1)-antitrypsin.

33 ically required for ubiquitination of mutant alpha1-antitrypsin, a luminal ERAD substrate.

34 evaluate the function of this loop, we used alpha1-antitrypsin, a non-heparin-binding serpin and slo

35 ction of a point mutation (Glu342Lys) in the alpha(1)-antitrypsin (A1AT, also known as SERPINA1) gene

36 bly, upon transplantation, human albumin and alpha1-antitrypsin (A1AT) in mouse sera secreted by enca

37 t expression of the human protease inhibitor alpha1-antitrypsin (A1AT) in Nicotiana benthamiana.

38 alpha1-Antitrypsin (A1AT) purified from human plasma upr

39 This study shows that human alpha1-antitrypsin (A1AT) upregulates expression and rel

40 alpha1-Antitrypsin (A1AT) was identified as a plasma pro

41 alpha(1)-Antitrypsin (AAT) deficiency is an underrecogni

42 of intravenous supplementation therapy with alpha(1)-antitrypsin (AAT) to reduce the rate of urinary

43 alpha1 -Antitrypsin (AAT) deficiency is one of the most

44 The rationale of alpha1-antitrypsin (AAT) augmentation therapy to treat p

45 Mutations in alpha1-antitrypsin (AAT) can cause the protein to polyme

46 alpha1-Antitrypsin (AAT) deficiency predisposes to bronc

47 alpha1-Antitrypsin (AAT) is a potent protease inhibitor,

48 alpha1-Antitrypsin (AAT) is a serpin, the primary functi

49 The serum protease inhibitor alpha1-antitrypsin (AAT) possesses antiinflammatory prop

50 istration of the serine proteinase inhibitor alpha1-antitrypsin (AAT) prevents type 1 diabetes develo

51 uble/insoluble distribution of two misfolded alpha1-antitrypsin (AAT) variants responsible for AAT de

52 We demonstrate that treatment with alpha1-antitrypsin (AAT), an agent that dampens inflamma

53 s were selected from the proteomic analysis, alpha1-antitrypsin (AAT), hemopexin (HX), and gelsolin (

54 For newly synthesized alpha1-antitrypsin (AAT), the modification of its aspara

55 A sulfated alpha1-antitrypsin (AAT), thought to be a default secret

56 -acidglycoprotein) and type II (haptoglobin, alpha1-antitrypsin) acute phase proteins.

57 as used to assess the digestive stability of alpha(1)-antitrypsin against pepsin and pancreatin.

58 Polymers of Z alpha(1)-antitrypsin aggregate within the liver leading

59 nt than occurs by passive diffusion of human alpha1-antitrypsin alone.

60 Deficiency of alpha(1) -antitrypsin (alpha(1) AT) may be a determinant

61 probe the mechanism of peptide modulation of alpha(1)-antitrypsin (alpha(1)-AT) polymerization and de

62 Because retention of mutant alpha(1)-antitrypsin (alpha(1)-AT) Z in the endoplasmic

63 ecific folding of the canonical serpin human alpha(1)-antitrypsin (alpha(1)-AT).

64 rrhosis and emphysema caused by mutations in alpha(1)-antitrypsin (alpha(1)AT), and thrombosis caused

65 conformational dynamics of the serpin human alpha(1)-antitrypsin (alpha(1)AT).

66 rs to the liver of an animal model for human alpha1-antitrypsin (alpha1-AT) deficiency.

67 alpha1-Antitrypsin (alpha1-AT) is a serum protease inhib

68 ription of three HNF-4alpha sensitive genes, alpha1-antitrypsin (alpha1-AT), transthyretin (TTR), and

69 pots specific to liver proteins: albumin and alpha1-antitrypsin (alpha1-AT).

70 are mainly expressed in the liver, including alpha1-antitrypsin, alpha1-antichymotrypsin, alpha-fetal

71 In alpha(1)-antitrypsin (alpha1AT) deficiency, a polymeroge

72 Point mutants of alpha1 -antitrypsin (alpha1AT) form ordered polymers tha

73 alpha1-Antitrypsin (alpha1AT) deficiency (alpha1ATD) is

74 s control region (LCR) upstream of the human alpha1-antitrypsin (alpha1AT) gene that is required for

75 Inhibitory activity of alpha1-antitrypsin (alpha1AT) toward elastase showed neg

76 (Glu342Lys) in the serine protease inhibitor alpha1-antitrypsin (alpha1AT), which is found in more th

77 serpin family: protein C inhibitor (PCI) and alpha1-antitrypsin (alpha1AT); however, both exhibit poo

78 The human gene encoding alpha1-antitrypsin (alpha1AT, gene symbol PI) resides in

79 ing of a known ERAD substrate, the Z form of alpha1-antitrypsin (alpha1AT-Z).

80 production could be recovered by addition of alpha1-antitrypsin, an endogenous inhibitor of serine pr

81 We determine the rigid subunits of alpha(1)-antitrypsin and analyse the changes in their re

82 The protease inhibitors alpha(1)-antitrypsin and antichymotrypsin are present in

83 The results suggest that alpha(1)-antitrypsin and antichymotrypsin are produced b

84 alpha(1)-Antitrypsin and antichymotrypsin concentrations

85 Alpha(1)-antitrypsin and antichymotrypsin concentrations

86 It has been hypothesized that alpha(1)-antitrypsin and antichymotrypsin may modulate d

87 )-antitrypsin and antichymotrypsin, measured alpha(1)-antitrypsin and antichymotrypsin throughout lac

88 termined whether the mammary gland expresses alpha(1)-antitrypsin and antichymotrypsin, measured alph

89 olymerase chain reaction to detect genes for alpha(1)-antitrypsin and antichymotrypsin.

90 We show here that monomers of plasma serpins alpha(1)-antitrypsin and antithrombin are stable on incu

91 he peptide prevented the polymerization of Z alpha(1)-antitrypsin and did not significantly anneal to

92 17Phe mutations stabilise the native fold of alpha(1)-antitrypsin and increase secretion of monomeric

93 tease inhibitor family of proteins including alpha(1)-antitrypsin and protein C inhibitor.

94 rotein secretion and secretion of endogenous alpha(1)-antitrypsin and serum albumin from HepG2 cells.

95 the reactive-site loop of antithrombin into alpha(1)-antitrypsin and tested the chimeras against thr

96 he degradation of two other ERAD substrates, alpha1-antitrypsin and deltaCD3.

97 diazole) was used to label peroxide-modified alpha1-antitrypsin and demonstrate that the Cys-232 in v

98 distended, with significant accumulation of alpha1-antitrypsin and GRP78.

99 se had measurements of fecal lactoferrin and alpha1-antitrypsin and underwent pouch endoscopy with bi

100 correlate well with immunological levels of alpha1-antitrypsin and, thus, may prove useful for asses

101 f two serine protease inhibitors [Serpina1a (alpha1-antitrypsin) and Elafin] was dysregulated in Fbln

102 enteropathy (calprotectin, myeloperoxidase, alpha1-antitrypsin) and the prevalence of bacterial but

103 sponse genes such as SERPINA1, which encodes alpha1 antitrypsin, and FOXP4, an inhibitor of mucus pro

104 itors of metalloproteinase 2, -3, and -4 and alpha1-antitrypsin, and fibrosis was associated with inc

105 R1, TNFR2, Bid), optimal IL-13 inhibition of alpha1-antitrypsin, and IL-13-induction of and activatio

106 molecules, the solubility of mutant forms of alpha1-antitrypsin, and interactions with newly synthesi

107 oembryonic antigen, retinol binding protein, alpha1-antitrypsin, and squamous cell carcinoma antigen-

108 termined levels of carcinoembryonic antigen, alpha1-antitrypsin, and squamous cell carcinoma antigen.

109 Serum levels of nine biomarkers (alpha1 antitrypsin, apolipoprotein CIII, brain-derived n

110 The S- and Z-deficiency alleles of alpha1-antitrypsin are found in more than 20% of some wh

111 tracellular serpins such as antithrombin and alpha1-antitrypsin are the quintessential regulators of

112 ave assessed a surface hydrophobic cavity in alpha1-antitrypsin as a potential target for rational dr

113 ts identifying cathepsin C, cathepsin Z, and alpha1-antitrypsin as additional potential cargoes for L

114 y, and levels of inflammatory biomarkers and alpha1-antitrypsin at baseline.

115 Alpha(1)-antitrypsin (AT) is the most abundantly circula

116 In the classical form of alpha1-antitrypsin (AT) deficiency, a point mutation in

117 hial epithelial cells with purified plasma M alpha1-antitrypsin attenuates this inflammatory response

118 echanism due to accumulation of the mutant Z alpha1-antitrypsin (ATZ) and is a key example of an dise

119 alpha(1)-Antitrypsin blocked FNf-induced shedding of CD4

120 nzymes retain vulnerability to inhibition by alpha(1)-antitrypsin, but demonstrate variable avidity f

121 Replacement of His-334 in alpha(1)-antitrypsin by a serine or alanine at pH 7.4 re

122 mutation reduces concentrations in serum of alpha1 antitrypsin by retaining polymerised molecules wi

123 educed the intracellular polymerization of Z alpha1-antitrypsin by 60%.

124 reduced the intracellular accumulation of Z alpha1-antitrypsin by 70% in a cell model of disease.

125 biomarkers, followed by IL-2 receptor alpha, alpha1-antitrypsin, C-reactive protein, YKL-40, cellular

126 inhibited by alpha(1)-proteinase inhibitor (alpha(1)-antitrypsin), C1 inhibitor, and most efficientl

127 Polymers of mutant alpha1-antitrypsin can also form within the alveoli and

128 ility of the GeneSwitch, we cloned the human alpha(1)-antitrypsin cDNA into the optimal lentiviral ve

129 An alpha1-antitrypsin chimera harboring the P3-P2' residues

130 The alpha1-antitrypsin chimera with inhibitory characteristi

131 f interleukin-6, interleukin-8, and elastase-alpha1-antitrypsin complexes compared with presurgery le

132 f interleukin-8, interleukin-6, and elastase-alpha1-antitrypsin complexes were elevated compared with

133 ls of interleukin-6, interleukin-8, elastase-alpha1-antitrypsin complexes, thrombin-antithrombin comp

134 Treatment with the serine protease inhibitor alpha1-antitrypsin decreased serum levels of HS, leading

135 Alpha1-antitrypsin defciency-related liver disease is th

136 ith severe, early-onset COPD (without severe alpha(1)-antitrypsin deficiency) and 348 of their first-

137 result from mutations in the genes SERPINA1 (alpha(1)-antitrypsin deficiency), JAG1 (Alagille syndrom

138 In the classical form of alpha(1)-antitrypsin deficiency, a mutant protein accumu

139 as up-regulated in livers from patients with alpha(1)-antitrypsin deficiency, and the degree of up-re

140 The polymerization of AT, leading to alpha(1)-antitrypsin deficiency, has been studied extens

141 distinct form of "ER stress" that occurs in alpha(1)-antitrypsin deficiency, presumably determined b

142 6 male and 4 female former smokers, two with alpha(1)-antitrypsin deficiency.

143 rs that can be used to treat patients with Z alpha(1)-antitrypsin deficiency.

144 wn as SERPINA1) gene that is responsible for alpha(1)-antitrypsin deficiency.

145 y centres in 13 countries if they had severe alpha1 antitrypsin deficiency (serum concentration <11 m

146 sensitive measure of disease progression in alpha1 antitrypsin deficiency emphysema than spirometry

147 inhibitor (A1PI) augmentation treatment for alpha1 antitrypsin deficiency has not been substantiated

148 mphysema progression in patients with severe alpha1 antitrypsin deficiency in a randomised controlled

149 dividuals with emphysema secondary to severe alpha1 antitrypsin deficiency.

150 led trial of A1PI treatment in patients with alpha1 antitrypsin deficiency.

151 ng, is believed to cause lung destruction in alpha1-antitrypsin deficiency (AATD).

152 ive pulmonary disease (COPD) associated with alpha1-antitrypsin deficiency (AATD).

153 alpha1-Antitrypsin deficiency (ATD) is a common genetic

154 In the classical form of alpha1-antitrypsin deficiency (ATD), aberrant intracellu

155 r injury in patients with the classical form alpha1-antitrypsin deficiency (ATD).

156 verity and distribution in 119 subjects with alpha1-antitrypsin deficiency (PiZ phenotype) and groupe

157 Severe alpha1-antitrypsin deficiency (typically PiZZ homozygosi

158 Organoids from alpha1-antitrypsin deficiency and Alagille syndrome pati

159 studies of gene therapy for cystic fibrosis, alpha1-antitrypsin deficiency and lung cancer.

160 ng of genetic and nongenetic modifiers in ZZ alpha1-antitrypsin deficiency and other disorders of pro

161 the end-stage liver disease associated with alpha1-antitrypsin deficiency and underscore the contrib

162 he most frequent mutation that causes severe alpha1-antitrypsin deficiency arises in the SERPINA 1 ge

163 Severe alpha1-antitrypsin deficiency caused by the Z variant (G

164 ents with CF, primary ciliary dyskinesia, or alpha1-antitrypsin deficiency exhibited 3-fold higher mu

165 netic hemochromatosis, Wilson's disease, and alpha1-antitrypsin deficiency grow significantly.

166 Alpha1-antitrypsin deficiency is a genetic disease that

167 Alpha1-antitrypsin deficiency is a genetic disorder that

168 alpha1-Antitrypsin deficiency is an inherited condition

169 alpha1-Antitrypsin deficiency is one of the most common

170 The association of alpha1-antitrypsin deficiency with the development of em

171 netic disorders, such as cystic fibrosis and alpha1-antitrypsin deficiency, and for other diseases, i

172 Less common causes include hemochromatosis, alpha1-antitrypsin deficiency, autoimmune hepatitis, and

173 ess of augmentation therapy (Aug) for severe alpha1-antitrypsin deficiency, comparing strategies of:

174 abolic conditions studied in further detail (alpha1-antitrypsin deficiency, familial hypercholesterol

175 In alpha1-antitrypsin deficiency, intrahepatocyte accumulat

176 which underlies misfolding diseases such as alpha1-antitrypsin deficiency.

177 ding Gaucher disease, cystic fibrosis and ZZ alpha1-antitrypsin deficiency.

178 that underlies emphysema in individuals with alpha1-antitrypsin deficiency.

179 stemic inflammatory diseases associated with alpha1-antitrypsin deficiency.

180 apy for treatment of liver diseases, such as alpha1-antitrypsin deficiency.

181 tions in CF, primary ciliary dyskinesia, and alpha1-antitrypsin deficiency.

182 clinically and cost-effective therapies for alpha1-antitrypsin deficiency.

183 re, early-onset COPD probands without severe alpha1-antitrypsin deficiency.

184 The 2.2 A structure of Thr114Phe alpha(1)-antitrypsin demonstrates that the effects of th

185 ecognizes polymers formed by Z and His334Asp alpha(1)-antitrypsin despite the mutations directing the

186 ther hereditary iron overload disorders, and alpha1-antitrypsin disease-are the focus of this review.

187 se diseases are typified by the Z variant of alpha(1)-antitrypsin (E342K), which causes the retention

188 Mutant Z alpha1-antitrypsin (E342K) accumulates as polymers withi

189 equence corresponding to residues 359-374 of alpha1-antitrypsin, enhances gene expression from DNA na

190 ns are connected to the main ER network in Z-alpha1-antitrypsin-expressing cells.

191 oligosaccharides, sorts terminally misfolded alpha(1)-antitrypsin for proteasome-mediated degradation

192 Z and shutter domain mutants of alpha(1)-antitrypsin form polymers with a shared epitope

193 are identical to the Z-deficiency variant of alpha(1)-antitrypsin form urea-stable polymers in vivo.

194 eatments for emphysema, infusion of purified alpha1 antitrypsin from pooled human plasma represents a

195 of an 8-kb DNA segment upstream of the human alpha1-antitrypsin gene yields a mutant serpin allele th

196 The Z mutant of alpha1-antitrypsin (Glu342Lys) causes a domain swap and

197 Donor hepatocytes were derived from human alpha(1)-antitrypsin (hAAT) transgenic mice of the FVB s

198 mutations such as emphysema caused by human alpha1 antitrypsin (hAAT) deficiency.

199 Human alpha1-antitrypsin (hAAT) is an antiinflammatory, immune

200 Third, a mutant allele of human alpha1-antitrypsin (hAAT) was linked to Fah and resulted

201 gents, monotherapy with clinical-grade human alpha1-antitrypsin (hAAT), the major serum serine-protea

202 eactive protein, alpha(1)-acid glycoprotein, alpha(1)-antitrypsin, haptoglobin, and fibrinogen concen

203 e fractional and absolute synthesis rates of alpha(1)-antitrypsin, haptoglobin, and fibrinogen were m

204 The Z mutant of alpha(1)-antitrypsin has a point mutation Glu342Lys in t

205 opology.Here we compare the conformations of alpha(1)-antitrypsin in native and cleaved states.

206 Both mutations increase the secretion of Z alpha(1)-antitrypsin in the native conformation, but the

207 educe the polymerisation of wild-type native alpha(1)-antitrypsin in vitro and increase secretion in

208 pidly inactivated by the human plasma serpin alpha(1)-antitrypsin in vitro, administration of recombi

209 This is best described for the Z variant of alpha(1)-antitrypsin in which the proinflammatory proper

210 denoassociated virus vector expressing human alpha1-antitrypsin in murine liver progenitor cells.

211 re derived, such as aggregation of misfolded alpha1-antitrypsin in the endoplasmic reticulum, deficie

212 e accumulation of the misfolded Z variant of alpha1-antitrypsin in the hepatocyte endoplasmic reticul

213 obtained in SU5416-treated rats given human alpha1-antitrypsin intravenously.

214 alpha(1)-Antitrypsin is a serine protease inhibitor secr

215 Alpha(1)-antitrypsin is the most abundant circulating pr

216 Although alpha1 antitrypsin is mainly produced in the liver, its

217 alpha1-Antitrypsin is a serine protease inhibitor produc

218 findings have indicated that a deficiency in alpha1-antitrypsin is associated with increased risk of

219 ellular portion of the pIgR, linked to human alpha1-antitrypsin is effectively ferried across human t

220 Overexpression of Z alpha1-antitrypsin is known to induce polymer formation,

221 nd a novel shutter domain mutant (His334Asp; alpha(1)-antitrypsin King's) identified in a 6-week-old

222 disease, whereas low levels of circulating Z alpha1-antitrypsin lead to emphysema by loss of inhibiti

223 hepsin C and cathepsin Z in liver lysates or alpha1-antitrypsin levels in plasma.

224 alpha(1)-Antitrypsin may survive digestion and may affec

225 cal production of polymers by mutant S and Z alpha1-antitrypsin may have also provided protection aga

226 in addition to its antielastolytic effects, alpha1-antitrypsin may have broader biological effects i

227 n-originated cells expressing liver-specific alpha1-antitrypsin messenger RNA, albumin and hepatocyte

228 lt in a conformational transition within the alpha1-antitrypsin molecule and the formation of polymer

229 alcium ionophore, or when a nonpolymerogenic alpha(1)-antitrypsin mutant accumulated in the ER.

230 se protective, proinflammatory properties of alpha1-antitrypsin mutants have become detrimental to ca

231 y, intrahepatocyte accumulation of defective alpha(1)-antitrypsin occurs.

232 ts were effective at ratios of compound to Z alpha1-antitrypsin of 2.5:1 and reduced the intracellula

233 helium protease is not highly susceptible to alpha1-antitrypsin or secretory leukocyte protease inhib

234 olecular level structural information on the alpha(1)-antitrypsin polymer.

235 the generation of an mAb (4B12) that blocked alpha1-antitrypsin polymerization in vitro at a 1:1 mola

236 urin and PC6 with the serpin-based inhibitor alpha(1) antitrypsin Portland.

237 substrate decanoyl-RVKR-chloromethylketone, alpha1-antitrypsin Portland and by its own propeptide.

238 study, we show that inducible expression of alpha1-antitrypsin Portland, a furin inhibitor, inhibits

239 Lactoferrin, with alpha(1)-antitrypsin present, was digested by pancreatin

240 ific promoter (murine albumin enhancer/human alpha1-antitrypsin promoter) further enhanced transgene

241 tutively active FoxO1 in the liver using the alpha1-antitrypsin promoter.

242 lation of the TGF-beta signaling pathway and alpha1-antitrypsin protein (a serine protease inhibitor)

243 e disease, inefficient secretion of a mutant alpha1-antitrypsin protein (AAT-Z) results in its accumu

244 of these regions in neuroserpin relative to alpha(1)-antitrypsin provides a basis for neuroserpin's

245 rAAV-human alpha1-antitrypsin (rAAV-hAAT) vectors were delivered by

246 His334Asp alpha(1)-antitrypsin rapidly forms polymers that accumul

247 ummary, this work provides new insights into alpha1-antitrypsin reactivity in oxidizing environments

248 rophils in the alveoli of individuals with Z alpha(1)-antitrypsin-related emphysema.

249 ssue destruction that is characteristic of Z alpha(1)-antitrypsin-related emphysema.

250 ion of emphysema in some individuals despite alpha(1)-antitrypsin replacement therapy.

251 ion of structural alveolar cell apoptosis by alpha1-antitrypsin represents a novel protective mechani

252 The common Z mutant (Glu342Lys) of alpha(1)-antitrypsin results in the formation of polymer

253 de, a circulating bioactive peptide from the alpha1-antitrypsin serine protease inhibitor.

254 ssociated with HLA-DP and the genes encoding alpha(1)-antitrypsin (SERPINA1) and proteinase 3 (PRTN3)

255 -fold; apolipoprotein A-1 [APOA1], 3.2-fold; alpha1-antitrypsin [SERPINA1], 2.5-fold; and complement

256 s containing an immobile matrix of polymeric alpha1-antitrypsin, small ER resident proteins can diffu

257 Ab technology to identify interactors with Z alpha1-antitrypsin that comply with both requirements.

258 tify a peptide corresponding to a portion of alpha1-antitrypsin that potently inhibits entry of HIV-1

259 intrabody also increased the secretion of Z alpha1-antitrypsin that retained inhibitory activity aga

260 Relative to alpha(1)-antitrypsin, the reactive site loop of AT has t

261 but did increase the levels of mRNA encoding alpha1-antitrypsin, tissue inhibitor of metalloproteinas

262 proteolysis, and determined the potential of alpha(1)-antitrypsin to affect the survival of other mil

263 The transition of native Z alpha(1)-antitrypsin to polymers inactivates its anti-pr

264 ughout lactation, assessed the resistance of alpha(1)-antitrypsin to proteolysis, and determined the

265 tissue and the high risk of patients lacking alpha1-antitrypsin to develop emphysema, much interest h

266 rved multiply charged states at m/z 72,160 ([alpha1-antitrypsin + trypsin + H](+)) and 86,585 ([IgG +

267 atrix for the detection of several proteins (alpha1-antitrypsin, trypsin, IgG, protein G) and their c

268 86,585 ([IgG + protein G + 2H](2+)) for the alpha1-antitrypsin-trypsin and IgG-protein G complexes,

269 detection of weak protein complexes, such as alpha1-antitrypsin-trypsin and IgG-protein G complexes,

270 rate at which N-linked glycans of misfolded alpha1-antitrypsin variant NHK were trimmed.

271 NTS, AND MAIN RESULTS: Transduction of human alpha1-antitrypsin via replication-deficient adeno-assoc

272 still intact after digestion, but only when alpha(1)-antitrypsin was added.

273 This conformational difference from M alpha(1)-antitrypsin was exploited with a 6-mer reactive

274 After in vitro digestion, much of the alpha(1)-antitrypsin was still intact, whereas many othe

275 ggested that a significant fraction of their alpha(1)-antitrypsin was tied up in high molecular mass

276 Fecal alpha1-antitrypsin was not able to distinguish symptomat

277 errant form of the hepatic secretory protein alpha1-antitrypsin was stably expressed in a human embry

278 addition, transgene expression (serum human alpha1-antitrypsin) was sustained for the length of the

279 ch corresponds to Met(358), the P(1) site of alpha1-antitrypsin, was the inhibitory site for elastase

280 he P6-P1 region of the reactive site loop of alpha(1)-antitrypsin were constructed.

281 noassociated virus 1-vector-expressing human alpha1 antitrypsin were transplanted into the liver of m

282 tive-to-latent transition of another serpin, alpha1-antitrypsin, which does not readily go latent.

283 commonest pathogenic gene mutation yields Z-alpha1-antitrypsin, which has a propensity to self-assoc

284 alpha1-Antitrypsin, which is a metastable and conformati

285 2E1 (CYP2E1) by measuring the expression of alpha1-antitrypsin, which is controlled by these promote

286 Unlike other serpins such as alpha(1)-antitrypsin, wild-type neuroserpin will polymer

287 Wild-type alpha(1)-antitrypsin will form polymers upon incubation

288 A variant of alpha(1)-antitrypsin with an E342K (Z) mutation (ATZ) ha

289 t of soluble secretory proteins (albumin and alpha1-antitrypsin) with that of supramolecular cargoes

290 ation of polymers underlies the retention of alpha(1)-antitrypsin within hepatocytes and of neuroserp

291 e to inactivation by protein C inhibitor and alpha(1)-antitrypsin yet maintained their primary antico

292 ve indicated that the accumulation of mutant alpha(1)-antitrypsin Z in the ER specifically activates

293 related with the hepatic levels of insoluble alpha(1)-antitrypsin Z protein.

294 ays a critical role in disposal of insoluble alpha(1)-antitrypsin Z.

295 the fate of the misfolded secretory protein alpha1 antitrypsin Z.

296 tracellular accumulation of misfolded mutant alpha1-antitrypsin Z (ATZ) in hepatocytes causes hepatic

297 characterized by accumulation of the mutant alpha1-antitrypsin Z (ATZ) variant inside cells, causing

298 Intracellular accumulation of misfolded alpha1-antitrypsin Z in respiratory epithelial cells of

299 modifiers affecting the accumulation of the alpha1-antitrypsin Z mutant (ATZ) in a Caenorhabditis el

300 transgenic for the common misfolded variant alpha1-antitrypsin Z, is a model of respiratory epitheli