Paradoxical ATP elevation in ischemic penumbra revealed by quantitative imaging mass spectrometry.
Local responses of energy metabolism during brain ischemia are too heterogeneous to decipher redox distribution between anoxic core and adjacent salvageable regions such as penumbra. Imaging mass spectrometry combined by capillary electrophoresis/mass spectrometry providing quantitative metabolomics revealed spatio-temporal changes in adenylates and NADH in a mouse middle-cerebral artery occlusion model. Unlike the core where ATP decreased, the penumbra displayed paradoxical elevation of ATP despite the constrained blood supply. It is noteworthy that the NADH elevation in the ischemic region is clearly demarcated by the ATP-depleting core. Results suggest that metabolism in ischemic penumbra does not respond passively to compromised circulation, but actively compensates energy charges.
Hattori
Katsuji
K
Department of Biochemistry, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
Kajimura
Mayumi
M
Hishiki
Takako
T
Nakanishi
Tsuyoshi
T
Kubo
Akiko
A
Nagahata
Yoshiko
Y
Ohmura
Mitsuyo
M
Yachie-Kinoshita
Ayako
A
Matsuura
Tomomi
T
Morikawa
Takayuki
T
Nakamura
Tomomi
T
Setou
Mitsutoshi
M
Suematsu
Makoto
M
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002545:Brain Ischemia / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000503:physiopathology; D004195:Disease Models, Animal; D019075:Electrophoresis, Capillary; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology; D013058:Mass Spectrometry; D051379:Mice; D010084:Oxidation-Reduction; D015398:Signal Transduction
D000255:Adenosine Triphosphate