title: Transferred inter-cell ischemic preconditioning-induced neuroprotection may be mediated by adenosine A1 receptors.
abstract: Ischemic preconditioning-induced neuroprotection is a well-known phenomenon. We hypothesize that this form of neuroprotection is transferable among the same type of cells. To test this hypothesis, human neuroblastoma SH-SY5Y cells were induced to become neuron-like cells. Primary rat cortical neuronal cultures were also used. These cells were subjected to various lengths of short oxygen-glucose deprivation (OGD, an in vitro simulation of ischemia) and then 1-h OGD. Some cells that were not exposed to a short episode of ischemia were incubated with culture medium from the cells that had 3- or 5-min OGD. Those cells were subjected to OGD for 1h at 1 or 24h after they were exposed to the medium. Cell injury was evaluated at 24h after the 1-h OGD by lactate dehydrogenase release assay. In another experiment, cells subjected to a 3-min OGD or exposed to the medium from cells that had a 3-min OGD were harvested at 30min after the OGD or the medium exposure for Western blotting of Akt, a prosurvival protein. Our study showed that a prior episode of ischemia lasting from 3 to 10min significantly reduced the 1-h OGD-induced cell injury. Medium from cells subjected to a 3-min OGD also induced acute and delayed phases of neuroprotection in OGD-naïve human neuron-like cells and primary rat cortical neuronal cultures. Cells subjected to a 3-min OGD or incubated with the medium from cells exposed to a 3-min OGD had increased phosphorylated/activated Akt. The increased phosphorylated Akt and neuroprotection induced by medium transferring were inhibited by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A1 receptor inhibitor. The 3-min OGD-induced neuroprotection was inhibited by LY294002, an Akt activation inhibitor. These results suggest that ischemic preconditioning-induced neuroprotection is transferable among the cells. Small molecules, such as adenosine, may mediate this effect.
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, United States; Department of Anesthesiology, Research Institute and Hospital, National Cancer Center, Republic of Korea.
authors.forename: Jungyeon
authors.initials: J
authors.lastname: Yun
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, United States; Department of Anesthesiology, Fourth Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, United States. Electronic address: zz3c@virginia.edu.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply*; D045744:Cell Line, Tumor; D006801:Humans; D019194:Ischemic Preconditioning; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D043682:Receptor, Adenosine A1 / Q000378:metabolism*
chemical_list: D043682:Receptor, Adenosine A1; D007770:L-Lactate Dehydrogenase
keywords: Adenosine A1 receptor; Akt; Inter-cell preconditioning; Neuroprotection