Multidrug resistance proteins in tuberous sclerosis and refractory epilepsy.
Tuberous sclerosis is an autosomal dominant syndrome characterized by seizures that are refractory to medication in severely affected individuals. The mechanism involved in drug resistance in tuberous sclerosis is unknown. The proteins MDR-1 (multidrug resistance) and MRP-1 (multidrug resistance-associated protein-1) are linked to chemotherapy resistance in tumor cells. However, the relationship between refractoriness to antiepileptic drugs and MDR-1 or MRP-1 brain expression has been poorly studied. We have previously described a case of tuberous sclerosis with refractory epilepsy that expressed multidrug resistance gene (MDR-1) in tuber cells from epileptogenic brain lesion. In this retrospective study, we describe the expression of MDR-1 and MRP-1 in the epileptogenic cortical tubers of three pediatric patients with tuberous sclerosis and refractory epilepsy surgically treated. Monoclonal antibodies for MDR-1 and MRP-1 proteins were used for immunohistochemistry. In epileptogenic cortical tuber brain specimens, MDR-1 and MRP-1 proteins were strongly immunoreactive in abnormal balloon cells, dysplastic neurons, astrocytes, microglial cells, and some blood-brain vessels. A more extensive MDR-1 immunoreactivity was observed. These data suggest that refractory epilepsy phenotype in tuberous sclerosis can be associated with the expression of both multidrug resistance MDR-1 and MRP-1 transporters in epileptogenic cortical tubers.
Lazarowski
Alberto
A
Clinical Biochemistry Department, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Argentina.
Lubieniecki
Fabiana
F
Camarero
Sandra
S
Pomata
Hugo
H
Bartuluchi
Marcelo
M
Sevlever
Gustavo
G
Taratuto
Ana Lía
AL
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis / Q000737:chemistry; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000737:chemistry; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D018432:Drug Resistance, Multiple; D004827:Epilepsy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis* / Q000737:chemistry; D012189:Retrospective Studies; D014402:Tuberous Sclerosis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1