Protection of hepatocytes from apoptosis by a novel substance from actinomycetes culture medium.
A novel substance, #675, found from an Streptomyces sp. SM675 culture medium, dose-dependently stimulates the proliferation of human functional liver cell 4 (FLC4). When FLC4 cells were incubated under conditions without fetal bovine serum (FBS), typical features of apoptotic cell death such as shrinkage and nuclear condensation appeared; high molecular weight (HMW) DNA fragments were found; and caspase-3 and poly (ADP-ribose) polymerase (PARP) proteins were cleaved. When FLC4 cells were incubated with #675 and without FBS, the cells grew healthy, no HMW DNA fragments were found, and caspase-3 and PARP cleavage weakened, suggesting that #675 protects FLC4 cells from apoptosis induced by FBS-deprivation. The quantitative reverse-transcribed polymerase chain reaction did not show differences in PARP or Bcl-2 mRNA expression in FLC4 cells incubated with or without #675, indicating other genes may be involved in this anti-apoptosis effect. These results show that #675 enhances FLC4 proliferation via an apoptosis-inhibition pathway, implying potential pharmacological and clinical applications.
Liu
Yang
Y
Department of Biochemistry, School of Medicine, Akita University, 1-1-1 Hondo, Akita 010-8543, Japan.
Takahashi
Saori
S
Ogasawara
Hironobu
H
Seo
Han Geuk
HG
Kawagoe
Masami
M
Hirasawa
Fujiko
F
Guo
Naxin
N
Ueno
Yasuharu
Y
Kameda
Takashi
T
Sugiyama
Toshihiro
T
D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003470:Culture Media; D053938:DNA Fragmentation / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D019254:Genes, bcl-2 / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007564:Japan; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012988:Soil Microbiology; D013302:Streptomyces / Q000737:chemistry* / Q000302:isolation & purification
D003470:Culture Media; D018076:DNA, Complementary; D012333:RNA, Messenger; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases