In anemia zinc is recruited from bone and plasma to produce new red blood cells

Chen, Yen-Hua; Jeng, Sen‐Shyong; Hsu, Ya-Chia; Liao, Yu-Min; Wang, Yuxin; Cao, Xia; Huang, Lian-Jiang

doi:10.1016/j.jinorgbio.2020.111172

Cited by 15 publications

(13 citation statements)

References 39 publications

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“…Tokuyama divided 312 patients with CKD into two groups with a serum Zn concentration of 60 µg/dL as the threshold, and survival analysis showed Zn deficiency was a risk factor for ESKD or death ( 63 ). The possible causes of decreased plasma Zn levels in patients with CKD are as follows: Decreased absorption of Zn from the gastrointestinal tract; limited Zn intake; higher urinary Zn excretion; and redistribution of Zn in the body ( 64 ). Zn is associated with anemia, cardiovascular disease, and repair of kidney damage in patients with CKD ( Figure 2 ).…”

Section: Discussionmentioning

confidence: 99%

Benefits and risks of essential trace elements in chronic kidney disease: a narrative review

Xie¹,

Liu²,

Zhang³

et al. 2022

Ann Transl Med

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Background and Objective: Chronic kidney disease (CKD) is an important public health concern.With the decline of renal function, CKD patients gradually progress to end-stage kidney disease and need to undergo dialysis or kidney transplantation to maintain life, bringing a heavy economic burden to the family and society. Therefore, it is necessary to effectively prevent and delay the progression of CKD. Essential trace elements play an indispensable role in CKD, and the objective of this study is to systematically review their benefits in the disease and summarize the risks of their excess.Methods: The keywords "trace elements", "chronic kidney disease", "dialysis", "inflammation", and "fibrosis" and their combinations were used to search for relevant literature published in the PubMed database and Web of Science. We then summarized the role of trace element abnormalities in CKD patients in anemia, oxidative stress, inflammation, and chronic fibrosis, and the risk of their excess.

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Section: Discussionmentioning

confidence: 99%

Benefits and risks of essential trace elements in chronic kidney disease: a narrative review

Xie¹,

Liu²,

Zhang³

et al. 2022

Ann Transl Med

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“…It is also important to note that many CKD patients are elderly and using multiple medications that can affect taste sensation and increase zinc deficiency [ 38 ]. In a recent study by Chen et al, 5/6 nephrectomized rats as well as phenylhydrazine-induced anemic mice were found to have zinc redistributed to bone marrow from bone and plasma, causing the zinc level in plasma to decrease, which produced reticulocytes [ 39 ]. Their novel findings of pools of zinc in plasma and bone redistributed to bone marrow in the majority of those nephrectomized rats indicate the mechanism of zinc deficiency in CKD.…”

Section: Zinc Deficiency In Ckdmentioning

confidence: 99%

Association of Zinc Deficiency with Development of CVD Events in Patients with CKD

et al. 2021

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Deficiency of the micronutrient zinc is common in patients with chronic kidney disease (CKD). The aim of this review is to summarize evidence presented in literature for consolidation of current knowledge regarding zinc status in CKD patients, including those undergoing hemodialysis. Zinc deficiency is known to be associated with various risk factors for cardiovascular disease (CVD), such as increased blood pressure, dyslipidemia, type 2 diabetes mellitus, inflammation, and oxidative stress. Zinc may protect against phosphate-induced arterial calcification by suppressing activation of nuclear factor kappa light chain enhancer of activated B. Serum zinc levels have been shown to be positively correlated with T50 (shorter T50 indicates higher calcification propensity) in patients with type 2 diabetes mellitus as well as those with CKD. Additionally, higher intake of dietary zinc was associated with a lower risk of severe abdominal aortic calcification. In hemodialysis patients, the beneficial effects of zinc supplementation in relation to serum zinc and oxidative stress levels was demonstrated in a meta-analysis of 15 randomized controlled trials. Thus, evidence presented supports important roles of zinc regarding antioxidative stress and suppression of calcification and indicates that zinc intake/supplementation may help to ameliorate CVD risk factors in CKD patients.

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“…In the bone marrow of rats, zinc assimilation was observed in the condition of increased erythropoietic demand due to hemolytic anemia [ 3 ]. Redistribution of zinc was reported in anemic mice and rats, leading to elevated bone marrow and erythrocyte zinc [ 39 ]. Additionally, upregulation of the zinc importer ZIP10 and downregulation of the exporter ZnT1 in the plasma membrane fraction of mature red blood cells by dietary zinc restriction have been demonstrated in mice [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Cellular Zinc Deficiency Impairs Heme Biosynthesis in Developing Erythroid Progenitors

2023

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Anemia is the most prevalent nutrition-related disorder worldwide. Zinc is an essential trace element for various biological processes in the body, and zinc deficiency has been associated with anemia in humans. However, the molecular mechanisms by which zinc availability alters red blood cell development remain uncertain. The present study identifies the essentiality of zinc during erythroid development, particularly for normal heme biosynthesis. G1E-ER4 mouse cells were used as an in vitro model of terminal erythroid differentiation, which featured elevated cellular zinc content by development. Restriction of zinc import compromised the rate of heme and α-globin production and, thus, the hemoglobinization of the erythroid progenitors. Heme is synthesized by the incorporation of iron into protoporphyrin. The lower heme production under zinc restriction was not due to changes in iron but was attributable to less porphyrin synthesis. The requirement of adequate zinc for erythroid heme metabolism was confirmed in another erythropoietic cell model, MEL-DS19. Additionally, we found that a conventional marker of iron deficiency anemia, the ZnPP-to-heme ratio, responded to zinc restriction differently from iron deficiency. Collectively, our findings define zinc as an essential nutrient integral to erythroid heme biosynthesis and, thus, a potential therapeutic target for treating anemia and other erythrocyte-related disorders.

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In anemia zinc is recruited from bone and plasma to produce new red blood cells

Cited by 15 publications

References 39 publications

Benefits and risks of essential trace elements in chronic kidney disease: a narrative review

Benefits and risks of essential trace elements in chronic kidney disease: a narrative review

Association of Zinc Deficiency with Development of CVD Events in Patients with CKD

Cellular Zinc Deficiency Impairs Heme Biosynthesis in Developing Erythroid Progenitors

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