Expression and cellular distribution of multidrug resistance-related proteins in patients with focal cortical dysplasia.
Recent arouse of interest indicated that drug resistant proteins are markedly over-expressed in the epileptogenic tissue and they may be responsible for the one-third of the epileptic patients who were refractory to anti-epileptic drugs (AEDs). Since several AEDs may act as substrates for these drug resistant proteins, the enhanced function of such proteins may increase drug extrusion, resulting in inadequate response to drug therapy in patients with epilepsy. We studied expression of the multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1) in the epileptic tissues resected surgically in 28 patients with focal cortical dysplasia (FCD) by immunohistochemistry. The results were compared with 10 normal necropsy brain tissues. Normal brain showed no MDR1 expression in neurons and astrocytes, while MRP1 expression was very weak, which were encountered in a few samples. MDR1 expression was mainly localized on the vascular endothelial cells. In contrast to normal brain, we found intense MDR1 and MRP1 expression in both neurons and reactive astrocytes in the vast majority of dysplastic tissues. The majority of the dysplastic neurons demonstrated moderate to strong MRP1 immunoreactivity. Endothelial cells showed both MDR1 and MRP1 expression in the majority of the specimens studied. Multidrug transporters are over-expressed in the epileptogenic zone in patients with FCD. These results are concordant with previous studies, in which over-expression of multidrug proteins were shown in epileptogenic brain tissue in patients with FCD, that the over-expression of drug transport proteins in tissue from patients with refractory epilepsy may explain one possible mechanism for drug resistant in these pathologies.
Ak
Halil
H
Istanbul University, Cerrahpasa Medical Faculty, Department of Neurosurgery, Istanbul, Turkey.
Ay
Bahadir
B
Tanriverdi
Taner
T
Sanus
Galip Zihni
GZ
Is
Merih
M
Sar
Mehmet
M
Oz
Buge
B
Ozkara
Cigdem
C
Ozyurt
Emin
E
Uzan
Mustafa
M
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D001253:Astrocytes / Q000378:metabolism; D001927:Brain Diseases / Q000150:complications / Q000473:pathology*; D002540:Cerebral Cortex / Q000002:abnormalities / Q000378:metabolism* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000378:metabolism; D004827:Epilepsy / Q000150:complications / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D018709:Statistics, Nonparametric
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513055:ABCB1 protein, human; C421109:multidrug resistance-associated protein 1