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rno‐miR‐665 targets BCL 2L1 (Bcl‐xl) and increases vulnerability to propofol in developing astrocytes
Author(s) -
Sun WenChong,
Pei Ling
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13647
Subject(s) - propofol , in vivo , hippocampal formation , apoptosis , blot , neuroprotection , gene knockdown , pharmacology , andrology , biology , microbiology and biotechnology , chemistry , endocrinology , medicine , gene , biochemistry
Propofol exerts a cytotoxic influence over immature neurocytes. Our previous study revealed that clinically relevant doses of propofol accelerated apoptosis of primary cultured astrocytes of developing rodent brains via rno‐miR‐665 regulation. However, the role of rno‐miR‐665 during the growth spurt of neonatal rodent brains in vivo is still uncertain. Post‐natal day 7 (P7) rats received a single injection of propofol 30 mg/kg intraperitoneally ( i.p .), and neuroapoptosis of hippocampal astrocytes was analyzed by immunofluorescence and scanning electron microscopy. The differential expression of rno‐miR‐665, BCL 2L1 (Bcl‐xl), and cleaved caspase 3 ( CC 3) was surveyed by qRT ‐ PCR and western blotting. In addition, the utility of A‐1155463, a highly potent and BCL 2L1‐selective antagonist, was aimed to assess the contribution of BCL 2L1 for neuroglial survival. Following the intraventricular injection of lentivirus rno‐miR‐665, neuroprotection was detected by 5‐point scale measurement. The single dose of propofol 30 mg/kg triggered dose‐dependent apoptosis of developing hippocampal astrocytes. Meanwhile, propofol triggered both rno‐miR‐665 and CC 3, and depressed BCL 2L1 , which was predicted as one target gene of rno‐miR‐665. Combination treatment with A‐1155463 and propofol induced lower mRNA and protein levels of BCL 2L1 and more CC 3 activation than propofol treatment alone in vivo . The lentivirus‐mediated knockdown of rno‐miR‐665 elevated BCL 2L1 and attenuated CC 3 levels, whereas up‐regulation of rno‐miR‐665 suppressed BCL 2L1 and induced CC 3 expression in vivo . More importantly, rno‐miR‐665 antagomir infusion improved neurological outcomes of pups receiving propofol during the brain growth spurt. Rno‐miR‐665, providing a potential target for alternative therapeutics for pediatric anesthesia, is susceptible to propofol by negatively targeting antiapoptotic BCL 2L1 .Relatively little is known about the association between exposure of astrocytes to brief propofol anaesthesia and risk for impairment. Here, it revealed that propofol‐related neurotoxicity of neonatal astrocytes was under rno‐miR‐665 regulation during the brain growth spurt. Rno‐miR‐665 might act as a clinically alternative therapeutic target for treatment of neurological disorders in peadiatric anesthesia or sedation with propofol in future.