Human brain cortex: mitochondrial oxidative damage and adaptive response in Parkinson disease and in dementia with Lewy bodies.
Frontal cortex samples from frozen human brains were used to assess tissue respiration; content of mitochondria; mitochondrial oxygen uptake; activity of respiratory complexes and of mitochondrial nitric oxide synthase (mtNOS); content of cytochromes a, b, and c; oxidative damage (protein carbonyls and TBARS); and expression of Mn-SOD in patients with Parkinson disease (PD) and with dementia with Lewy bodies (DLB) in comparison with those of normal healthy controls. Brain cortex and mitochondrial O(2) uptake and complex I activity were significantly lower in PD and DLB, whereas mtNOS activity, cytochrome content, expression of Mn-SOD, mitochondrial mass, and oxidative damage were significantly higher in the frontal cortex in PD and DLB. The decreases in tissue and mitochondrial O(2) uptake and in complex I activity are considered the consequences of mitochondrial oxidative damage. The increases in mtNOS activity and in mitochondrial mass are interpreted as an adaptive response of the frontal cortex that involves increased NO signaling for mitochondrial biogenesis. The adaptive response would partially compensate for mitochondrial dysfunction in these neurodegenerative diseases and would afford a human evolutionary response to shortage of ATP in the frontal cortex.
Navarro
Ana
A
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Cádiz, 11003 Cádiz, Spain. ana.navarro@uca.es
Boveris
Alberto
A
Bández
Manuel J
MJ
Sánchez-Pino
María Jesús
MJ
Gómez
Carmen
C
Muntané
Gerard
G
Ferrer
Isidro
I
D000368:Aged; D000369:Aged, 80 and over; D003573:Cytochrome b Group / Q000737:chemistry / Q000378:metabolism; D003574:Cytochrome c Group / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D010101:Oxygen Consumption / Q000502:physiology*; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology
D003573:Cytochrome b Group; D003574:Cytochrome c Group; D019001:Nitric Oxide Synthase