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Regulatory effect of hydrogen sulfide on endoplasmic reticulum stress and lipid metabolism in livers in apoE knockout mice / 中华老年医学杂志
Chinese Journal of Geriatrics ; (12): 1356-1360, 2013.
Article in Chinese | WPRIM | ID: wpr-439287
ABSTRACT
Objective To investigate the regulatory effect of hydrogen sulfide (H2S) on endoplasmic reticulum stress (ERS) and lipid metabolism in livers in apoE knockout (apo E-/-) mice.Methods Male C57BL/6 J mice and homozygous apoE mice were fed with a western type diet and randomly divided into four groupsC57BL/6 J control group (injected intraperitoneally with normal saline),apoE group (injected intraperitoneally with normal saline),apoE-/-+NaHS group (injected intraperitoneally with an H2S donor NaHS 56μmol · kg-1 · d-1) and apoE-/-+ DL-propargylglycine (PPG) group (injected intraperitoneally with an acystathionine-γ-lyase inhibitor PPG 30 mg ·kg-1 · d-1).After 10 weeks,all mice were sacrificed and plasma lipids were detected.Lipid deposition was determined by oil red O staining.Glucose-regulated protein78 (GRP78),Thr-981 phosphorylated double-stranded RNA-activated protein kinase like endoplasmic reticulum kinase (PERK),subunit of eukaryotic translation initiation factor-2α (elF-2α),low density lipoprotein (LDL) receptor (LDLR),sterol regulatory element binding protein-2 (SREBP-2) in the livers were detected by Western bloting.The expressions of GRP78 and SREBP-2 mRNA were analyzed by realtime polymerase chain reaction (RT-PCR).Results Compared with C57BL/6 J control group,plasma levels of total cholesterol (TC),triglyceride (TG) and low density lipoprotein (LDL),liver lipid content and expressions of GRP-78,PERK and eIF-2α were significantly increased in apoE-/-mice,but body weight did not change.Compared with apoE-/-mice,plasma LDL level was decreased,liver lipid deposition was improved,expressions of GRP-78 and PERK in livers were increased,and the ratio of p-eIF-2α/ eIF-2α was increased in apoE-/-+NaHS group,but expression levels of SREBP-2 and LDLR in liver did not change.Conclusions H2S decreases serum LDL level and liver lipid content,and up regulates GRP78 protein and mRNA expressions,promotes PERK and eIF2α phosphorylations,improves endoplasmic reticulum function,but has no effect on the expressions of SREBP-2 and LDLR in apoE-/-mice fed with a high-fat diet.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Geriatrics Year: 2013 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Geriatrics Year: 2013 Type: Article