Differential effects of sublethal ischemia and chemical preconditioning with 3-nitropropionic acid on protein expression in gerbil hippocampus.
Pretreatment with a low dose of 3-nitropropionic acid (3-NPA) has been shown to induce ischemic tolerance in the gerbil hippocampus. It is well known that sublethal (2-min) ischemia also induces ischemic tolerance. To investigate the acquisition of ischemic tolerance with 3-NPA, we examined the protein expression after 3-NPA treatment in comparison with sublethal ischemia. Immunohistochemical studies revealed intense expression of Bcl-2 and Bcl-xL in the hippocampal CA1 area after 3-NPA treatment. Furthermore, the time course of the expression of Bcl-xL showed a similar pattern to the acquisition of ischemic tolerance by 3-NPA treatment. The induction of Bcl-xL occurred in the hippocampal CA1 area at 24 h after 3-NPA treatment, and significant induction was observed at 48 h. Western blot analysis of hippocampus harvested 48 h after the pretreatment, showed that the expression of Bcl-2 and Bcl-xL was significantly increased by either 3-NPA treatment or 2-min ischemia. However, PMCA1 and HSP70 protein expression increased only in the sublethal ischemia treated group. The difference between 3-NPA treated group and control group was not statistically significant. These results suggest that Bcl-2 and Bcl-xL are essential for acquisition of ischemic tolerance, while HSP70 and PMCA1 play important roles in the enhancement of ischemic tolerance.
Kato
Kengo
K
The Second Department of Internal Medicine, Nippon Medical School, 1-1-5 Bunkyo-ku, Sendagi, Tokyo, 113-8603, Japan. katoken@ms2.jichi.ac.jp
Shimazaki
Kuniko
K
Kamiya
Tatsushi
T
Amemiya
Shimon
S
Inaba
Toshiki
T
Oguro
Keiji
K
Katayama
Yasuo
Y
D000222:Adaptation, Physiological; D000818:Animals; D015153:Blotting, Western; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005849:Gerbillinae; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007124:Immunoenzyme Techniques; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009574:Nitro Compounds; D053499:Plasma Membrane Calcium-Transporting ATPases; D011422:Propionates / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051020:bcl-X Protein
D027682:Cation Transport Proteins; D018840:HSP70 Heat-Shock Proteins; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D053499:Plasma Membrane Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; C015392:3-nitropropionic acid