Coxsackievirus B3 infection affects metal-binding/transporting proteins and trace elements in the pancreas in mice.
OBJECTIVE
The trigger of juvenile diabetes has been suggested to be an interaction between a virus and trace elements, where enteroviruses, including coxsackievirus B3 (CVB3), have been discussed as potential initiators. The aim of this study was to investigate the effects in the pancreas on gene expressions of metallothionein 1 (MT1), divalent metal transporter 1 (DMT1), and zinc transporter 5 (ZnT-5) and concomitant changes in iron (Fe), copper (Cu), and zinc (Zn) in serum and pancreas of Balb/c mice on days 3, 6, and 9 of CVB3 infection.


METHODS
Trace elements were measured through inductively coupled plasma-mass spectrometry, and CVB3, MT1, DMT1, and ZnT-5 were measured by reverse transcription-polymerase chain reaction.


RESULTS
Virus was found in the pancreas on all days, with a peak on day 3. Infection tended to increase Fe in both serum and the pancreas. The Cu/Zn ratio in the pancreas increased early in the infection because of a great decrease in Zn. In serum, the Cu/Zn ratio was not increased until day 9 of the disease. In the pancreas, MT1 decreased, whereas DMT1 tended to increase on day 6, and ZnT-5 increased progressively during the course of the disease.


CONCLUSIONS
Virus-induced changes in trace elements, MT1, DMT1, and ZnT-5 in the pancreas may reflect early stages of the development of pancreatitis and prestages of diabetic disease.
Frisk
Peter
P
Research in Metal Biology, Rudbeck Laboratory, Uppsala University, Sweden. peter.frisk@kemi.uu.se
Tallkvist
Jonas
J
Gadhasson
Inga-Lill
IL
Blomberg
Jonas
J
Friman
Göran
G
Ilbäck
Nils-Gunnar
NG
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology; D018450:Disease Progression; D029822:Enterovirus B, Human / Q000302:isolation & purification / Q000472:pathogenicity*; D004769:Enterovirus Infections / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D007501:Iron / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010179:Pancreas / Q000378:metabolism* / Q000821:virology; D014131:Trace Elements / Q000378:metabolism*; D014766:Viremia / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000378:metabolism; D000099236:Solute Carrier Family 11, Member 2
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D003300:Copper; D007501:Iron; D026901:Membrane Transport Proteins; D008668:Metallothionein; D014131:Trace Elements; D015032:Zinc; D000099236:Solute Carrier Family 11, Member 2; C486753:Slc30a5 protein, mouse; C407523:metallothionein isoform 1