Cathepsin K generates enkephalin from beta-endorphin: a new mechanism with possible relevance for schizophrenia.
Recent studies associate cathepsin K with schizophrenia. The endogenous substrates of this protease, however, remain to be identified. We show here that cathepsin K is capable of liberating met-enkephalin from beta-endorphin (beta-EP) in vitro. To verify if this process might possibly contribute in the pathogenesis of schizophrenia post mortem brains of patients suffering from this disease were analysed immunohistochemically for the presence and co-localization of cathepsin K and beta-EP. In support of a functional role of the observed formation of met-enkephalin on the expense of beta-EP increased numbers of cathepsin K immunoreactive cells, but diminished numbers of both beta-EP-positive cells and double-positive (cathepsin K/beta-EP) cells were found in left and right arcuate nucleus of schizophrenics. In addition a reduced density of beta-EP-immunoreactive neuropil (fibres, nerve terminals) was estimated in the left and right paraventricular nucleus (PVN) of individuals with schizophrenia. Our results imply that cathepsin K, which becomes up-regulated in its cerebral expression by neuroleptic treatment, might significantly contribute to altered opioid levels in brains of schizophrenics, which have previously been reported by us and others, and might reinforce the interest in the putative roles of endorphin and enkephalins in neuropsychiatric disorders.
Lendeckel
Uwe
U
Institute of Experimental Internal Medicine, University of Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany. uwe.lendeckel@uni-greifswald.de
Kähne
Thilo
T
Ten Have
Sara
S
Bukowska
Alicja
A
Wolke
Carmen
C
Bogerts
Bernhard
B
Keilhoff
Gerburg
G
Bernstein
Hans-Gert
HG
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004744:Enkephalin, Methionine / Q000096:biosynthesis*; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D001615:beta-Endorphin / Q000378:metabolism*
D014150:Antipsychotic Agents; D012333:RNA, Messenger; D004744:Enkephalin, Methionine; D001615:beta-Endorphin; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; D006220:Haloperidol