Selective translocation of diacylglycerol kinase zeta in hippocampal neurons under transient forebrain ischemia.
The molecular mechanisms responsible for differential neuronal vulnerability to ischemic injury are incompletely understood. Previous studies have reported that the expression and activity of protein kinase C (PKC), some subtypes of which are activated by Ca(2+) and diacylglycerol (DG), are altered after ischemic insults. Therefore, DG kinase (DGK), which is responsible for controlling PKC activity through DG metabolism, may also be involved in this process. DGKzeta, which is abundantly expressed in the brain, contains a nuclear localization signal (NLS), suggesting its involvement in some nuclear processes in neuronal cells. To elucidate the functional implications of DGKzeta in ischemia, we examined detailed localization of DGKzeta in rat brain after ischemic insults. We used an ischemic model of global cerebral ischemia for 20 min by bilateral common carotid artery occlusion combined with hypotension and followed time-points of reperfusion. DGKzeta expression was evaluated by immunohistochemistry using affinity-purified anti-DGKzeta antibody. In sham-operated rats, a strong DGKzeta-immunoreactivity was observed in the nucleus of neurons in various parts of the brain. In the global ischemic model DGKzeta-immunoreactivity was reduced in intensity in the hippocampal formation and detected in the cytoplasm of CA1 pyramidal neurons throughout reperfusion time courses. Change in the subcellular localization was restricted to the pyramidal cells in CA1 and later in CA3, but not observed in other areas of hippocampus. No change was observed in the cerebral and cerebellar cortices. The present study suggests that DGKzeta might be involved in the process of selective vulnerability of hippocampal pyramidal neurons in postischemic brain.
Ali
Hasmat
H
Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Iida-nishi 2-2-2, Yamagata 990-9585, Japan.
Nakano
Tomoyuki
T
Saino-Saito
Sachiko
S
Hozumi
Yasukazu
Y
Katagiri
Yuji
Y
Kamii
Hideyuki
H
Sato
Shinya
S
Kayama
Takamasa
T
Kondo
Hisatake
H
Goto
Kaoru
K
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000502:physiology; D019852:Diacylglycerol Kinase / Q000235:genetics*; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D019585:Intracranial Hypotension / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000201:enzymology*; D018613:Microscopy, Confocal; D009474:Neurons / Q000201:enzymology*; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism
D019852:Diacylglycerol Kinase