Multidrug resistance proteins in tuberous sclerosis and refractory epilepsy.

Abstract

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.

• Authors: Alberto Lazarowski, Fabiana Lubieniecki, Sandra Camarero, Hugo Pomata, Marcelo Bartuluchi, Gustavo Sevlever, Ana Lía Taratuto
• Journal: Pediatric neurology (Pediatr Neurol) Vol. 30 Issue 2 Pg. 102-6 (Feb 2004) ISSN: 0887-8994 [Print] United States
• PMID: 14984901 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Multidrug Resistance-Associated Proteins
• multidrug resistance-associated protein 1

Topics

• ATP Binding Cassette Transporter, Subfamily B (biosynthesis, chemistry)
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (biosynthesis, chemistry)
• Cerebral Cortex (metabolism, pathology, surgery)
• Drug Resistance, Multiple
• Epilepsy (metabolism, pathology, surgery)
• Humans
• Multidrug Resistance-Associated Proteins (biosynthesis, chemistry)
• Retrospective Studies
• Tuberous Sclerosis (metabolism, pathology, surgery)