Calcium increases apolipoprotein B mRNA editing.
ApoB-100 and apoB-48 are major components of chylomicrons, very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL). The two proteins are generated from a single apoB mRNA by apoB mRNA editing which induces an in-frame stop codon in apoB mRNA. Apolipoprotein B (apoB) mRNA editing is an important determinant of the proportion of full-length (apoB-100) and truncated (apoB-48) proteins in total apoB metabolism. Calcium is involved in the regulation of secretion and synthesis of VLDL and apoB. In this paper, we demonstrate for the first time that the amount of edited apoB mRNA in the cultured cells Caco-2 and McA7777 is markedly increased by calcium. Increasing extracellular calcium concentration, calcium ionophore (A23187 and ionomycin) treatment, and depleting calcium stores and raising cytoplasmic calcium concentration by thapsigargin increase apoB mRNA editing up to threefold in a dose dependent manner. Calcium has no direct stimulative effect on apoB mRNA editing in an in vitro editing system. The editing increase by extracellular calcium is not related to alterations of APOBEC-1 mRNA expression. These data suggest that calcium is not only involved in the regulation of apolipoprotein metabolism but also apoB mRNA editing.
Chen
Z
Z
National Heart, Lung and Blood Institute, Bethesda, Maryland, 20892, USA.
Eggerman
T L
TL
Potosky
D
D
Arborati
M
M
Patterson
A P
AP
D000071479:APOBEC-1 Deaminase; D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics*; D018938:Caco-2 Cells; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D003564:Cytidine Deaminase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D017393:RNA Editing / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D001055:Apolipoproteins B; D012333:RNA, Messenger; D000001:Calcimycin; D015759:Ionomycin; D019284:Thapsigargin; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605091:Apobec1 protein, rat; D003564:Cytidine Deaminase; D002118:Calcium