Endoplasmic reticulum thiol oxidase deficiency leads to ascorbic acid depletion and noncanonical scurvy in mice.
Endoplasmic reticulum thiol oxidase deficiency leads to ascorbic acid depletion and noncanonical scurvy in mice.
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内质网硫醇氧化酶缺乏会导致小鼠抗坏血酸耗竭和非范围的坏血病。
DOI：
10.1016/j.molcel.2012.08.010
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发表时间：
2012-10-12
期刊：
影响因子：
16
通讯作者：
Ron, David
中科院分区：
文献类型：
--
作者：
Zito, Ester;Hansen, Henning Gram;Yeo, Giles S. H.;Fujii, Junichi;Ron, David
Endoplasmic reticulum (ER) thiol oxidases initiate a disulfide relay to oxidatively fold secreted proteins. We found that combined loss-of-function mutations in genes encoding the ER thiol oxidases ERO1α, ERO1β, and PRDX4 compromised the extracellular matrix in mice and interfered with the intracellular maturation of procollagen. These severe abnormalities were associated with an unexpectedly modest delay in disulfide bond formation in secreted proteins but a profound, 5-fold lower procollagen 4-hydroxyproline content and enhanced cysteinyl sulfenic acid modification of ER proteins. Tissue ascorbic acid content was lower in mutant mice, and ascorbic acid supplementation improved procollagen maturation and lowered sulfenic acid content in vivo. In vitro, the presence of a sulfenic acid donor accelerated the oxidative inactivation of ascorbate by an H2O2-generating system. Compromised ER disulfide relay thus exposes protein thiols to competing oxidation to sulfenic acid, resulting in depletion of ascorbic acid, impaired procollagen proline 4-hydroxylation, and a noncanonical form of scurvy. ► Abnormal extracellular matrix in mice compromised in their ER thiol oxidases ► Abnormal procollagen maturation responsive to ascorbate repletion ► Tissue ascorbate depletion and noncanonical scurvy in the mutant mice
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DOI：
10.1073/pnas.53.2.335
发表时间：
1965-01-01
影响因子：
11.1
作者：
PETERKOFSKY, B;UDENFRIEND, S
通讯作者：
UDENFRIEND, S
影响因子：
--
作者：
Klomsiri, Chananat;Nelson, Kimberly J.;Bechtold, Erika;Soito, Laura;Johnson, Lynnette C.;Lowther, W. Todd;Ryu, Seong-Eon;King, S. Bruce;Furdui, Cristina M.;Poole, Leslie B.
通讯作者：
Poole, Leslie B.
影响因子：
16
作者：
Frand, AR;Kaiser, CA
通讯作者：
Kaiser, CA
影响因子：
16
作者：
Pollard, MG;Travers, KJ;Weissman, JS
通讯作者：
Weissman, JS
影响因子：
10.5
作者：
Marciniak, SJ;Yun, CY;Ron, D
通讯作者：
Ron, D