Abstract OBJECTIVE: GRP78 is a sensitive marker of endoplasmic reticulum stress. Caspase-12 is involved in apoptosis induced by endoplasmic reticulum stress. This study was designed to explore the changes of GRP78 and caspase-12 mRNA in neonatal rats with experimental hypoxic-ischemic white matter damage (WMD) and investigate the roles of endoplasmic reticulum stress in the WMD. METHODS: Two-day-old rats were randomized to WMD and control groups (n=49 each). The pups were sacrificed at 0, 2, 4, 6, 12, 24 and 72 hrs after hypoxia-ischemia (HI). The light microscope was used to observe the brain pathological changes. Real time PCR was used to detect the expression of GRP78 mRNA and caspase-12 mRNA in the white matter tissue. RESULTS: The expression of GRP78 mRNA began increasing 2 hrs after HI and peaked at 6 hrs in the WMD group, demonstrating significant differences at 2, 4, 6, 12, 24 and 72 hrs compared with the control group (P<0.05). The caspase-12 mRNA expression in the WMD group began increasing 6 hrs after HI and demonstrated significantly increased levels 6, 12 and 24 hrs after HI compared with those in the control group (P<0.05). CONCLUSIONS: GRP78 and caspase-12 mRNA expression increased significantly in neonatal rats with WMD. This suggests that endoplasmic reticulum stress may be induced following HI. Endoplasmic reticulum stress seems to be involved in the apoptosis of oligodendrocytes induced by HI in neonatal rats with WMD.［Chin J Contemp Pediatr, 2009, 11 (8):691-694］
LUO Li-Li,XIONG Ying,WANG Hui-Qing. Expression of GRP78 and caspase-12 in neonatal rats with experimental hypoxic-ischemic white matter damage[J]. 中国当代儿科杂志, 2009, 11(08): 691-694.
LUO Li-Li,XIONG Ying,WANG Hui-Qing. Expression of GRP78 and caspase-12 in neonatal rats with experimental hypoxic-ischemic white matter damage[J]. CJCP, 2009, 11(08): 691-694.
［1］Blumenthal I. Periventricular leucomalacia: a review ［J］. Eur J Pediatr, 2004, 163(8):435-442.
［2］Mouw G, Zechel JL, Gamboa J, Lust WD, Selman WR, Ratcheson RA. Activation of caspase-12, an endoplasmic reticulum resident caspase, after permanent focal ischemia in rat［J］. Neuroreport, 2003, 14(2):183-186.
［3］Back SA, Han BH, Luo NL, Chricton CA, Xanthoudakis S, Tam J, et al. Selective vulnerability of late oligodendrocyte progenitors to hypoxiaischemia［J］. J Neurosci, 2002, 22(2):455-463.
［4］Craig A, Ling Luo N, Beardsley DJ, Wingate-Pearse N, Walker DW, Hohimer AR, et al. Quantitative analysis of perinatal rodent oligodendrocyte lineage progression and its correlation with human［J］. Exp Neurol, 2003, 181(2):231-240.
［5］Luo S, Mao C, Lee B, Lee AS. GRP78/BiP is required for cell proliferation and protecting the inner cell mass from apoptosis during early mouse embryonic development［J］. Mol Cel Biol, 2006, 26(15):5688-5697.
［6］Back SA. Perinatal white matter injury: The changing spectrum of pathology and emerging insights into pathogenetic mechanisms ［J］. Ment Retard Dev Disabil Res Rev, 2006, 12(2):129-140.
［7］Li F, Hayashi T, Jin G, Deguchi K, Nagotani S, Nagano I, et al. The protective effect of dantrolene on ischemic neuronal cell death is associated with reduced expression of endoplasmic reticulum stress markers［J］. Brain Res, 2005, 1048(1-2):59-68.
［8］Ito D, Tanaka K, Suzuki S, Dembo T, Kosakai A, Fukuuchi Y. Up-regulation of the Ire1-mediated signaling molecule, Bip, in ischemic rat brain［J］. Neuroreport, 2001, 12(18):4023-4028.
［9］Vilatoba M, Eckstein C, Bilbao G, Smyth CA, Jenkins S, Thompson JA, et al. Sodium 4-phenylbutyrate protects against liver ischemia reperfusion injury by inhibition of endoplasmic reticulum-stress mediated apoptosis ［J］. Surgery, 2005, 138(2):342-351.
［10］Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta ［J］. Nature, 2000, 403(6765):98-103.
［11］Reijonen S, Putkonen N, N-rrem-lle A, Lindholm D, Korhonen L. Inhibition of endoplasmic reticulum stress counteracts neuronal cell death and protein aggregation caused by N-terminal mutant huntingtin proteins［J］. Exp Cell Res, 2008, 314(5):950-960.
