Decreased expression of phospholipase C-beta 1 protein in endoplasmic reticulum stress-loaded neurons.
The endoplasmic reticulum (ER) plays a critical role in the maintenance of intracellular homeostasis and its dysfunction is thought to lead to neuronal death, which results in neurodegenerative disorders. Since phospholipase C (PLC) isozymes are involved in maintenance of the intracellular Ca2+ concentration by regulating Ca2+ release from the ER, their expression might be affected by ER stress. Of these isozymes, PLC-beta 1 and -gamma 1, in particular, are known to protect cells from oxidative stress and thus alteration of their expression profile under ER stress-loaded conditions is interesting. Using primary cultured rat cortical neurons, we here examined whether expression of PLC-beta 1 and -gamma 1 was altered in ER stress-loaded neurons induced by tunicamycin (Tm). In ER stress-loaded neurons treated with Tm in the range of 0.03-3 microg/ml for 20 h, the viability of the neurons was decreased dose-dependently, the decrease being significant with 0.3 or more microg/ml, and expression of the representative ER stress markers, GRP78/BiP, and cleaved caspase-3 and -12, was increased after 24 h postincubation, confirming the induction of ER stress in the neurons. In the ER stress-loaded neurons obtained on Tm treatment, the expression level of PLC-beta 1 decreased dose-dependently. On the other hand, there was no difference in the PLC-gamma 1 protein expression level between control and ER stress-loaded neurons. Overall, we demonstrated that ER stress decreases the expression of PLC-beta 1, but not -gamma 1, in neurons.
Yasuda
Eri
E
Department of Environmental Biochemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Nagasawa
Kazuki
K
Nishida
Kentaro
K
Fujimoto
Sadaki
S
D000818:Animals; D015153:Blotting, Western; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D053454:Caspase 12 / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000201:enzymology*; D054799:Phospholipase C beta / Q000096:biosynthesis*; D051966:Phospholipase C gamma / Q000096:biosynthesis; D051381:Rats; D013312:Stress, Physiological / Q000201:enzymology*; D013778:Tetrazolium Salts; D019284:Thapsigargin / Q000494:pharmacology; D013844:Thiazoles; D014415:Tunicamycin / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D014415:Tunicamycin; D000001:Calcimycin; D019284:Thapsigargin; D054799:Phospholipase C beta; D051966:Phospholipase C gamma; D053454:Caspase 12; D053148:Caspase 3; C022616:thiazolyl blue; D002118:Calcium