Dynein c1h1, dynactin and syntaphilin expression in brain areas related to neurodegenerative diseases following exposure to rotenone.
Neurodegeneration is often accompanied by protein inclusions which may interfere with cell physiology. On the other hand, alteration in intracellular trafficking may precede impairment of neurotransmission and therefore trigger cell death. In view of this, it is hypothesized that changes in mitochondrial traffic may occur before neurodegeneration triggered by rotenone exposure and could favor this process. The effects of low concentrations of rotenone on the expression of dynein c1h1, dynactin and syntaphilin, which are proteins related to mitochondria transport and anchoring, were evaluated in cell cultures of substantia nigra, locus coeruleus and hippocampus as well as in these same brain areas in Lewis aged rats. The results indicate that low concentrations of rotenone decrease dynein c1h1 protein levels in cell cultures and brain areas of aged rats. Dynactin is decreased after exposure to 0.1 and 0.3 nM of rotenone, and increased after exposure to 0.5 nM of rotenone in cell cultures. Aged rats present increased dynactin expression. Syntaphilin expression decreased in vitro and increased in vivo after rotenone exposure. These findings suggest that changes in protein expression related to mitochondrial retrograde transport and anchoring occur before neurodegeneration induced by rotenone exposure, which may be a primary factor to trigger neurodegenerative mechanisms.
Department of Genetics and Evolutionary Biology, Institute for Biosciences, University of Sao Paulo, Sao Paulo, SP, Brazil, merari@usp.br.
Rodrigo S
RS
Chaves
Thaiany Q
TQ
Melo
Aline M
AM
D'Unhao
Karen L G
KLG
Farizatto
Merari F R
MFR
Ferrari
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012402:Rotenone / Q000494:pharmacology*
D002352:Carrier Proteins; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C000592961:Snph protein, rat; D012402:Rotenone; D004398:Dyneins