Lig-8, a bioactive lignophenol derivative from bamboo lignin, protects against neuronal damage in vitro and in vivo.
Lig-8, a lignophenol derivative from bamboo lignin, potently suppresses oxidative stress-induced apoptosis. Here, we first examined in vitro whether lig-8 protects against neuronal damage induced by oxygen-glucose deprivation (OGD) followed by reoxygenation, tunicamycin [endoplasmic reticulum (ER)-stress inducer], or PSI (proteasome inhibitor). In pheochromocytoma (PC12) cell cultures, lig-8 (1 to 30 microM) concentration-dependently inhibited OGD- and tunicamycin (2 microg/ml)-induced cell deaths (significant at >/=3 microM and >/=1 microM, respectively). In human neuroblastoma (SH-SY5Y) cell culture, the PSI-induced apoptotic cell death and fusion protein accumulation (revealing reduced proteasome activity) was inhibited by lig-8 (30 microM). On the other hand, lig-8 at 30 microM alone did not affect any proteasome activity under resting conditions. In vivo, lig-8 (0.1 nmol/eye) reduced intravitreal N-methyl-D-aspartate (NMDA, 20 nmol)-induced retinal damage (decreases in retinal ganglion cells and inner plexiform layer thickness). Hence, lig-8 protects, partly by inhibiting excessive ER-stress, against neuronal damage in vitro and in vivo.
Ito
Yasushi
Y
Department of Biofunctional Molecules, Gifu Pharmaceutical University, Japan.
Shimazawa
Masamitsu
M
Akao
Yukihiro
Y
Nakajima
Yoshimi
Y
Seki
Norio
N
Nozawa
Yoshinori
Y
Hara
Hideaki
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D031723:Bambusa / Q000737:chemistry*; D018929:Cell Culture Techniques; D004305:Dose-Response Relationship, Drug; D049452:Green Fluorescent Proteins / Q000032:analysis; D006801:Humans; D008031:Lignin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D016716:PC12 Cells; D061988:Proteasome Inhibitors; D051381:Rats; D012164:Retinal Diseases / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D014415:Tunicamycin / Q000494:pharmacology
C515659:Lig-8 compound; D018696:Neuroprotective Agents; D061988:Proteasome Inhibitors; D014415:Tunicamycin; D049452:Green Fluorescent Proteins; D008031:Lignin