Carbonyl stress: malondialdehyde induces damage on rat hippocampal neurons by disturbance of Ca(2+) homeostasis.
The objective of this study was to investigate the influences of carbonyl stress induced by malondialdehyde (MDA), a typical intermediate of lipid peroxidation, on intracellular free Ca(2+) concentration ([Ca(2+)](i)) alterations in cultured hippocampal neurons of rat. The microphotographic study clearly demonstrated that the hippocampal neurons became gradually damaged following exposure to different concentrations of MDA. Further study indicated that the plasma membrane Ca(2+)-ATPase (PMCA) activity was inhibited by MDA in a concentration- and time-dependent manner. The supplementation of 100 microM MDA was found to cause a notable early phase increase of [Ca(2+)](i) in hippocampal neuron cultures followed by a more pronounced late-phase elevation of [Ca(2+)](i). Such effect of MDA was prevented by the addition of nimodipine, an inhibitor of L-type calcium channel or by an extracellular Ca(2+) chelator EGTA. The identification of the calcium signalling pathways were studied by applying U73122, an inhibitor of PL-C, and H-89, an inhibitor of protein kinase A (PKA), showing the involvement of PL-C/IP3 pathway but not the PKA/cAMP pathway. These results suggested that MDA-related carbonyl stress caused damages of rat hippocampal neurons by triggering Ca(2+) influx and influencing Ca(2+) homeostasis in cultured neurons, and also MDA may act as a signalling molecule regulating Ca(2+) release from intracellular stores.
Cai
Jianguang
J
Hunan Normal University, Changsha, Hunan, People's Republic of China. pumacai@163.com
Chen
Jianguo
J
He
Hong
H
Yin
Zhaochu
Z
Zhu
Zerui
Z
Yin
Dazhong
D
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006706:Homeostasis; D008315:Malondialdehyde / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D008315:Malondialdehyde; D000252:Calcium-Transporting ATPases; D002118:Calcium