Shenfu injection on hypoxic-ischemic brain damage in neonatal rat ATF4
Hypoxic-ischemic brain damage (HIBD) occur in approximately 6 per 1,000 live births, 25% -30% of the survivors may leave some type of long-term sequelae. The study found that hypoxia, ischemia, low sugar, the ATP depletion, a large number of free radicals such as calcium overload can trigger endoplasmic reticulum stress (ERS), the start of the unfolded protein response (of UPR). Eukaryotic activate the transcription factor ([Only registered and activated users can see links. Click Here To Register...]) is the key factor of the PKR-like endoplasmic reticulum kinase (the PERK)-mediated UPR pathway. Shenfu injection main components of ginseng saponin and Aconitum alkaloids have a protective effect on brain injury.
But see note whether the injection from the cerebral protective effects by reducing the ERS, has yet to see the related reports.In the normal state, the PERK dimerization sites immunoglobulin binding protein (the Bip) cover, no endonuclease activity. ERS, a large number of Bip protein was used in conjunction with the unfolded protein PERK free, polymerization, phosphoric acid, so that the PERK itself to activate the substrate and catalyze eIF2 phosphorylation. Involved in mammalian cell protein translation initiation complex formation, eIF2 protein A, B, C, three kinds of subunits, A serine can be phosphorylated in. Phosphorylated eIF2 can inhibit the GDP-GTP exchange function, making the eIF2 can not be reused, reducing the start codon recognition rate, thus inhibiting protein synthesis in the boot process to reduce the level of translation. Although eIF2 phosphorylation lead to overall translational repression, but it can still specifically induced increase ATF4 mRNA translation. ATF4 expression, including the endoplasmic reticulum stress in cells is dependent on PERK-mediated eIF2 phosphorylation.ATF4 to regulate C / EBP homologous protein, growth arrest and DNA damage inducible protein 34 and activating transcription factor 3 (of ATF3) expression, which, of ATF3 also promote CHOP and GADD34 expression. CHOP and endoplasmic reticulum stress-induced apoptosis by down-regulating expression of Bcl-2 expression, increase Bim expression, depletion of glutathione, the promotion of ROS generation, activation of caspase-3, ultimately leading to cell apoptosis.Results found that the the HIBD ischemia in neonatal rat lateral prefrontal cortex of eIF2, ATF4 protein levels increase, showed that of eIF2, the ATF4 involved in the the HIBD pathological physiological processes. The HIBD likely to start the PERK-mediated UPR pathway.
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