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Zn deficiency promotes calcification in vascular smooth muscle cells independent of ALP action and in part by Pit1 up‐regulation
Author(s) -
Kwun InSook,
Alcantara Ethel H.,
Shin MeeYoung,
Beattie John H.
Publication year - 2013
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.27.1_supplement.860.8
Subject(s) - calcification , vascular smooth muscle , downregulation and upregulation , alkaline phosphatase , medicine , endocrinology , chemistry , nap , phosphate , phosphatase , biology , enzyme , biochemistry , smooth muscle , neuroscience , gene
Zn deficiency more recently has been related to the development of cardiovascular disease, which involves aberrant calcification. ALP is a key regulator in osteogenic calcification to increase local inorganic phosphate (Pi) concentration. Even though vascular smooth muscle cells (VSMCs) generally do not express alkaline phosphatase (ALP), its presence has been reported on calcified VSMCs. However, under Zn deficiency, our initial findings showed undetectable level of ALP activity in VSMCs at calcifying conditions. We therefore hypothesized that Zn deficiency‐induced calcification may not be initiated by ALP in VSMCs. To test this hypothesis, we cultured rat aortic A7r5 VSMCs using β‐glycerophosphate (β‐GP, as ALP substrate, 0–15 mM) or Na phosphate (NaP, as non‐ALP substrate, 0–7 mM) as source of Pi under Zn deficiency (1 μM) for up to 15 days to induce VSMC calcification. Under Zn deficiency, P and Ca accumulation (calcification) increased with increasing NaP concentration (3–7 mM) but not with β‐GP treatment in which requires ALP activity to generate Pi. ALP activity was neither affected by β‐GP nor by NaP concentrations. In addition, Zn status did not affect ALP activity in VSMCs. However, Pit1 as a sodium‐dependent phosphate transporter into the cells, was upregulated under zinc deficiency. Our findings illustrate that Zn deficiency‐induced calcification in VSMCs is not initiated by ALP action but in part by Pit1 upregulation. Supported by the fund of National Research Foundation of Korea (No. NRF‐2008–220‐F00013).