S-Adenosylhomocysteine (SAH) serves as an amino acid derivative and plays a regulatory role in various metabolic pathways, acting as an intermediate in the synthesis of cysteine and adenosine[1]. It inhibits the METTL3-METTL14 heterodimer complex (METTL3-14) with an IC50 of 0.9 µM[2].
体内研究
Administered via intravenous (i.v.), intraperitoneal (i.p.), or oral (p.o.) routes at dosages of 1-10 mg/kg, SAH has shown sleep-inducing and anticonvulsant effects in rabbits, rats, and cats[1].
When given as an intraperitoneal injection at a dose of 7 mg/kg one hour before sacrifice, SAH significantly increases the in vitro uptake of NE and 5-HT specifically in the brain stem and midbrain, but does not impact DA uptake[1].
体外研究
In concentrations ranging from 10^-7 to 10^-5 M, SAH enhances the in vitro uptake of norepinephrine (NE) and serotonin (5-HT) in rat brain synaptosomal preparations without affecting dopamine (DA) uptake[1].
Demonstrating potent inhibitory actions on METTL3-14 activity, SAH exhibits an IC50 value of 0.9 μM when evaluating the kinetic parameters of the METTL3-14 complex[2].
SAH 细胞实验
Cell Line
Concentration
Treated Time
Description
References
WRL68 cells
0.25 mM
2 hours
To investigate the effect of SAH or DZA pretreatment on TNF-induced cytotoxicity, results showed that SAH or DZA pretreatment significantly enhanced TNF cytotoxicity.
Biochem Pharmacol. 2007 Aug 1;74(3):521-31.
Primary rat hepatocytes
0.25 mM
2 hours
To investigate the effect of SAH or DZA pretreatment on TNF-induced cytotoxicity, results showed that SAH or DZA pretreatment significantly enhanced TNF cytotoxicity.
Biochem Pharmacol. 2007 Aug 1;74(3):521-31.
Human umbilical vein endothelial cells (HUVECs)
30 µM
48 hours
To investigate the effect of SAHH inhibition on vascular senescence, results showed that SAHH inhibition increased SA β-gal staining and expression of p16, p21, and p53.
Redox Biol. 2023 Sep;65:102828.
DU-145 cells
250 µM
6 days
To evaluate the effects of SAH on DU-145 cell proliferation, invasion, migration, and colony formation. Results showed that SAH treatment did not significantly affect DU-145 cell proliferation, invasion, migration, or colony formation.
Br J Pharmacol. 2015 Jun;172(11):2769-81.
PC-3 cells
250 µM
6 days
To evaluate the effects of SAH on PC-3 cell proliferation, invasion, migration, and colony formation. Results showed that SAH treatment did not significantly affect PC-3 cell proliferation, invasion, migration, or colony formation.
Br J Pharmacol. 2015 Jun;172(11):2769-81.
SAH 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Fox Chase SCID mice
Prostate cancer bone metastasis model
Intra-tibial injection
250 μM
Single injection, monitored for 4 weeks
To evaluate the effect of SAH treatment on PC-3 cell bone metastasis in mice. Results showed that SAH-treated PC-3 cells did not significantly differ from control in the formation of bone lesions.
搜索
