Mitochondrial extracellular signal-regulated kinases 1/2 (ERK1/2) are modulated during brain development.
Intracellular activation and trafficking of extracellular signal-regulated protein kinases (ERK) play a significant role in cell cycle progression, contributing to developmental brain activities. Additionally, mitochondria participate in cell signalling through energy-linked functions, redox metabolism and activation of pro- or anti-apoptotic proteins. The purpose of the present study was to analyze the presence of ERK1/2 in mitochondria during rat brain development. Immunoblotting, immune electron microscopy and activity assays demonstrated that ERK1/2 are present in fully active brain mitochondria at the outer membrane/intermembrane space fraction. Besides, it was observed that ERK1/2 translocation to brain mitochondria follows a developmental pattern which is maximal between E19-P2 stages and afterwards declines at P3, just before maximal translocation to nucleus, and up to adulthood. Most of mitochondrial ERK1/2 were active; upstream phospho-MAPK/ERK kinases (MEK1/2) were also detected in the brain organelles. Mitochondrial phospho-ERK1/2 increased at 1 microm hydrogen peroxide (H(2)O(2)) concentration, but it decreased at higher 50-100 microm H(2)O(2), almost disappearing after the organelles were maximally stimulated to produce H(2)O(2) with antimycin. Our results suggest that developmental mitochondrial activation of ERK1/2 cascade contributes to its nuclear translocation effects, providing information about mitochondrial energetic and redox status to the proliferating/differentiating nuclear pathways.
Alonso
Mariana
M
Institute of Cellular Biology and Neurosciences, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Melani
Mariana
M
Converso
Daniela
D
Jaitovich
Ariel
A
Paz
Cristina
C
Carreras
M Cecilia
MC
Medina
Jorge H
JH
Poderoso
Juan J
JJ
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000254:growth & development*; D001923:Brain Chemistry; D004789:Enzyme Activation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000201:enzymology
D016877:Oxidants; D006861:Hydrogen Peroxide; D011505:Protein-Tyrosine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D020929:Mitogen-Activated Protein Kinase Kinases