Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P42345 (
mTOR
)
26,049
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Oxidative stress is a crucial pathogenic factor in osteoporosis. Autophagy is a cellular self-digestion process that can selectively remove damaged organelles under oxidative stress, and thus presents a potential therapeutic target against osteoporosis.
Monotropein
is an iridoid glycoside which can increase osteoblastic bone formation and be applied for medicinal purpose in China. The aim of this work is to investigate whether autophagy participates the protection effects of monotropein in osteoblasts under oxidative stress and the possible mechanism of such involvement. Here, monotropein was capable of inhibiting the H
2
O
2
-induced reactive oxygen species generation in osteoblasts.
Monotropein
induced autophagy and protected osteoblasts from cytotoxic effects of H
2
O
2
, as assessed by viability assays, apoptosis and western blotting. Moreover, it significantly attenuated H
2
O
2
-evoked oxidative stress as measured by malondialdehyde, catalase, and superoxide dismutase levels. Importantly, monotropein reduced the phosphorylation of protein kinase B (Akt),
mammalian target of rapamycin
(
mTOR
) and its two downstream proteins (p70S6K and 4EBP1). The autophagy level increased in osteoblasts treated with monotropein as represented by an increased in both Beclin1 expression and the LC3-II/LC3-I ratio. However, the Akt activator (SC79) and
mTOR
activator (MHY1485) suppressed the autophagy level induced by monotropein in H
2
O
2
-treated cells. Consequently, the antioxidant effects of monotropein were mediated, at least in part, by enhancing autophagy through the Akt/
mTOR
pathway. These results suggested that monotropein might be a promising candidate for osteoporosis treatment.
...
PMID:Monotropein attenuates oxidative stress via Akt/mTOR-mediated autophagy in osteoblast cells. 3169 68
