RESUMO
Most infectious diseases are accompanied by a change in levels of several trace elements in the blood. However, it is not known whether changes in the gastrointestinal uptake of trace elements contribute to this event. Coxsackievirus B3 (CVB3), adapted to Balb/c mice, was used to study whether infection induces gene expression of metallothionein (MT1) and divalent-metal transporter 1 (DMT1) in the intestine and liver and hepcidin in the liver, as well as whether trace elements in these tissues are changed accordingly. Quantitative expression of CVB3, MT1, DMT1 and hepcidin was measured by real-time RT-PCR and six trace elements by ICP-MS on days 3, 6 and 9 of the infection. The copper/zinc (Cu/Zn) ratio in serum increased as a response to the infection. High concentrations of virus were found in the intestine and liver on day 3 and in the intestine on day 6. MT1 in the intestine and liver increased on days 3 and 6. The increase of MT1 in the liver correlated positively with Cu and Zn. Hepcidin in the liver showed a non-significant increase on days 3 and 6 of the infection, whereas DMT1 in the intestine decreased on day 9. Accordingly, iron (Fe) in the liver increased progressively during the disease, whereas in the intestine DMT1 was negatively correlated to Fe. Arsenic (As), cadmium (Cd) and mercury (Hg) were found to decrease to various degrees in the intestine, serum and liver. Thus, enteroviral infections, and possibly many other infections, may cause a change in the gastrointestinal uptake of both non-essential and essential trace elements.
Assuntos
Infecções por Coxsackievirus/metabolismo , Absorção Intestinal/fisiologia , Oligoelementos/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Cádmio/metabolismo , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Cobre/metabolismo , Enterovirus/metabolismo , Feminino , Células HeLa , Hepcidinas , Humanos , Mucosa Intestinal/metabolismo , Ferro/metabolismo , Fígado/metabolismo , Metalotioneína/genética , Metalotioneína/metabolismo , Camundongos , Camundongos Endogâmicos BALB CRESUMO
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.
Assuntos
Proteínas de Transporte/metabolismo , Enterovirus Humano B/patogenicidade , Infecções por Enterovirus/metabolismo , Pâncreas/metabolismo , Oligoelementos/metabolismo , Animais , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Cobre/metabolismo , Diabetes Mellitus Tipo 1/etiologia , Progressão da Doença , Enterovirus Humano B/isolamento & purificação , Infecções por Enterovirus/genética , Feminino , Regulação da Expressão Gênica , Ferro/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Metalotioneína/genética , Metalotioneína/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Pâncreas/virologia , Viremia/genética , Viremia/metabolismo , Zinco/metabolismoRESUMO
Autopsy of the brain has shown a change in trace element balance in some virus-infected individuals, but it is not known whether this event was a result of the infection. In the present study coxsackievirus B3 (CVB3) adapted to Balb/c mice was used to study whether infection induces gene expression of the metal-binding/transporting proteins metallothionein (MT1 and MT3) and divalent-metal transporter 1 (DMT1) and whether it changes the balance of trace elements in the brain. Virus and MT1, MT3, and DMT1 were quantitatively measured by RT-PCR on days 3, 6 and 9 of the infection. Trace elements (13) were measured in serum and the brain by ICP-MS. High numbers of virus were found in the brain on days 3 and 6, but virus counts were decreased and present only in 50% of the mice on day 9. Gene expression of MT1 tended to increase on all days, whereas that of MT3 only showed a minor and not significant increase on day 3. No clear effect was observed in the expression of DMT1. The increase of MT3 was correlated to the brain concentration of Cu. The Cu/Zn ratio in serum increased as a response to the infection. There was a similar decrease in Cd in serum and the brain. On day 6 of the infection, Hg increased in the brain (p<0.05) and was positively correlated to a concomitant decrease (p<0.05) in serum. Virus numbers in the brain were on day 6 positively correlated (p<0.05) to As concentrations. Enteroviral infections may therefore be an underlying factor regarding the changes in essential as well as potentially toxic trace elements in the brain.
