Both mild hypothermia and dopamine D(2) agonist are neuroprotective against hyperthermia-induced injury in PC12 cells.
We exposed rat pheochromocytoma PC12 cells to hyperthermia or high dosage of dopamine and examined the direct effects of mild hypothermia or dopamine D(2) receptor agonist. At a hyperthermia of 42-43 degrees C for 120 min there was approximately 50% loss of cell viability accompanied by dopamine overproduction. The model of cell death due to hyperthermia in PC12 cells belonged to the necrotic and late apoptotic population. At each temperature examined below 37 degrees C, significant decrease in cytotoxicity, the percentage of necrotic and late apoptotic cells, and dopamine overproduction were observed. Cytotoxicity could also be induced by high dosages of dopamine. Both hyperthermia and dopamine induced cytotoxicity in PC12 cells could also be reduced by dopamine D(2) agonists. These results indicate the dopamine is important in hyperthermic situations. The results also indicate that mild hypothermia and dopamine D(2) receptor agonists are neuroprotective against hyperthermia-induced brain injury.
Cheng
Bor-Chih
BC
Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan.
Chang
Ching-Ping
CP
Liu
Wen-Pin
WP
Lin
Mao-Tsun
MT
D000704:Analysis of Variance; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D001552:Benzazepines / Q000494:pharmacology; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000008:administration & dosage*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000628:therapy*; D007036:Hypothermia, Induced / Q000379:methods*; D008090:Lisuride / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D016716:PC12 Cells; D051381:Rats; D013696:Temperature; D013997:Time Factors
D017304:Annexin A5; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018696:Neuroprotective Agents; D008090:Lisuride; D004299:Dopamine beta-Hydroxylase; D004298:Dopamine