Tryptophan metabolism is dysregulated in individuals with Fanconi anemia

Author:

Bartlett Allison L.1,Romick-Rosendale Lindsey1,Nelson Adam1,Abdullah Sheyar1,Luebbering Nathan1,Bartlett Jamen2,Brusadelli Marion3,Palumbo Joseph S.4,Lake Kelly1,Litts Bridget1,Duell Alexandra1,Urbanski Annette1,Lane Adam1,Myers Kasiani C.1,Wells Susanne I.3,Davies Stella M.1

Affiliation:

1. Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH;

2. Southern Ohio Pathology Consultants, Cincinnati, OH; and

3. Division of Oncology and

4. Division of Hematology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH

Abstract

Abstract Fanconi anemia (FA) is a complex genetic disorder associated with progressive marrow failure and a strong predisposition to malignancy. FA is associated with metabolic disturbances such as short stature, insulin resistance, thyroid dysfunction, abnormal body mass index (BMI), and dyslipidemia. We studied tryptophan metabolism in FA by examining tryptophan and its metabolites before and during the stress of hematopoietic stem cell transplant (HSCT). Tryptophan is an essential amino acid that can be converted to serotonin and kynurenine. We report here that serotonin levels are markedly elevated 14 days after HSCT in individuals with FA, in contrast to individuals without FA. Kynurenine levels are significantly reduced in individuals with FA compared with individuals without FA, before and after HSCT. Most peripheral serotonin is made in the bowel. However, serotonin levels in stool decreased in individuals with FA after transplant, similar to individuals without FA. Instead, we detected serotonin production in the skin in individuals with FA, whereas none was seen in individuals without FA. As expected, serotonin and transforming growth factor β (TGF-β) levels were closely correlated with platelet count before and after HSCT in persons without FA. In FA, neither baseline serotonin nor TGF-B correlated with baseline platelet count (host-derived platelets), only TGF-B correlated 14 days after transplant (blood bank-derived platelets). BMI was negatively correlated with serotonin in individuals with FA, suggesting that hyperserotonemia may contribute to growth failure in FA. Serotonin is a potential therapeutic target, and currently available drugs might be beneficial in restoring metabolic balance in individuals with FA.

Publisher

American Society of Hematology

Subject

Hematology

Cited by 6 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3