Time course of changes in pyridoxal 5'-phosphate (vitamin B6 active form) and its neuroprotection in experimental ischemic damage.
In the present study, we investigated ischemia-induced changes of pyridoxal 5'-phosphate synthesizing enzyme and degrading enzyme and neuroprotective effects and roles of pyridoxal 5'-phosphate against ischemic damage in the gerbil hippocampal CA1 region. Pyridoxal 5'-phosphate oxidase and pyridoxal phosphate phosphatase immunoreactivities were changed in neurons up to 2 days after ischemia, while 4 days after ischemia their immunoreactivities were expressed in astrocytes. Pyridoxal 5'-phosphate oxidase immunoreactivity and its protein level were highest 12 h after ischemia, while those in pyridoxal phosphate phosphatase were highest 2 days after ischemia. Total activities of these enzymes were changed after ischemia, but specific activities of the enzymes were not altered. Treatment with pyridoxal 5'-phosphate into brains (4 microg/5 microl, i.c.v.) at 30 min before transient ischemia protected about 80% of CA1 pyramidal cells 4 days after ischemia and induced elevation of glutamic acid decarboxylase 67 immunoreactivity in the CA1 region. However, pyridoxal 5'-phosphate treatment into ischemic brains decreased GABA transaminase immunoreactivity in the CA1 region after ischemia. These results indicate that pyridoxal 5'-phosphate may be associated with the inhibitory discharge of GABA in the hippocampal CA1 neurons, and the increased level of GABA may protect hippocampal CA1 pyramidal cells from ischemic damage.
Hwang
In Koo
IK
Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon 200-702, South Korea.
Yoo
Ki-Yeon
KY
Kim
Do Hoon
DH
Lee
Bong-Hee
BH
Kwon
Young-Guen
YG
Won
Moo Ho
MH
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D020520:Brain Infarction / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005849:Gerbillinae; D005968:Glutamate Decarboxylase / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000096:biosynthesis* / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D007527:Isoenzymes; D018696:Neuroprotective Agents; D005680:gamma-Aminobutyric Acid; D011732:Pyridoxal Phosphate; D000445:Aldehyde Oxidoreductases; C034030:pyridoxal oxidase; D000612:4-Aminobutyrate Transaminase; C027138:pyridoxine phosphate phosphatase; D010744:Phosphoric Monoester Hydrolases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1