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Serum Copper Elevation Promotes Hepatic Ceruloplasmin Production and Excretion in Rat Model of Myocardial Infarction
Author(s) -
Yang Dan,
Wang Tao,
Zhang Jingyao,
Kang Y. James
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02022
Subject(s) - ceruloplasmin , medicine , myocardial infarction , endocrinology , excretion , ligation , homeostasis , copper , ischemia , cardiology , chemistry , organic chemistry
Ceruloplasmin (Cp) is a major copper‐binding protein in blood, regulating copper homeostasis. High levels of serum copper and Cp are both risk factors for coronary artery disease, particularly in patients with acute myocardial infarction. However, the relationship between the changes in serum copper and Cp levels in response to myocardial ischemia remains unknown. It is known that myocardial ischemia causes copper efflux from the heart leading to copper elevation in the blood. The present study was undertaken to test the hypothesis that the elevation of serum copper leads to an increase in hepatic Cp production and excretion. Adult male Sprague‐Dawley rats were subjected to left anterior descending (LAD) coronary artery ligation to induce myocardial infarction. Serum copper and Cp levels, as well as changes in hepatic Cp and copper‐transporting P‐type ATPase (ATP7B), were determined from blood and liver samples harvested on day 1, 4, or 7 after the operation. Serum copper concentrations were significantly increased on day 4 after LAD ligation, accompanied by an increase in serum Cp levels and activities. Concomitantly, the protein levels of Cp and copper exporter, ATP7B, were also significantly increased in the liver. Taken together, these results indicate that the elevated serum Cp levels mostly likely result from the increase in Cp production and excretion in the liver in response to the elevated serum copper levels following myocardial ischemia. Support or Funding Information West China Hospital, Sichuan UniversityChanges in hepatic Cp levels. At the time of 1, 4 or 7 day after LAD ligation, the liver tissues were harvested for Western blot and mRNA analysis. (A–C) Changes in hepatic Cp protein levels. (D–E) Changes in the expression of Cp, measured by RT‐PCR. Data are presented as mean ± SD, n=5–6, *P < 0.05. LAD: left anterior descending; MI: myocardial infarction.Changes in hepatic ATP7B levels. The sample preparation was as the same as presented in Figure 3. (A–C) Western blot analysis was performed to detect the protein level at different time point. (D–E) Changes in the expression of ATP7B, measured by RT‐PCR. Data are presented as mean ± SD, n=4–6, *P < 0.05. MI: myocardial infarction.