Abstract Objective To study the expression and effect of Pim1 in primary cortical neurons after hypoxic-ischemic injury. Methods Cortical neurons were isolated from 1-day-old C57BL/6 mice and cultured in neurobasal medium. On the 8th day of neuron culture, cells were subjected to oxygen-glucose deprivation/reoxygen (OGD/R) treatment to mimic in vivo hypoxic injury of neurons. Briefly, medium were changed to DMEM medium, and cells were cultured in 1% O2 for 3 hours and then changed back to normal medium and conditions. Cells were collected at 0 hour, 6 hours, 12 hours and 24 hours after OGD/R. Primary neurons were transfected with Pim1 overexpression plasmid or mock plasmid, and then were exposed to normal conditions or OGD/R treatment. They were named as Pim1 group, control group, OGD/R group and OGD/R+Pim1 group respectively. Real-time PCR was used to detect Pim1 mRNA expression. Western blot was used to detect the protein expression of Pim1 and apoptotic related protein cleaved caspase 3 (CC3). TUNEL staining was used to detect cell apoptosis. Results Real-time PCR and Western blot results showed that Pim1 mRNA and protein were significantly decreased in neurons after OGD/R. They began to decrease at 0 hour after OGD/R, reached to the lowest at 12 hours after OGD/R, and remained at a lower level at 24 hours after OGD/R (P P Conclusions Hypoxic-ischemic injury may decrease Pim1 expression in neurons. Overexpressed Pim1 may inhibit apoptosis induced by OGD/R.
LIU Jun-Yan,WANG Ke-Xuan,HUANG Ling-Yi et al. Expression and role of Pim1 in cultured cortical neurons with oxygen-glucose deprivation/reoxygen injury[J]. CJCP, 2020, 22(5): 512-518.
LIU Jun-Yan,WANG Ke-Xuan,HUANG Ling-Yi et al. Expression and role of Pim1 in cultured cortical neurons with oxygen-glucose deprivation/reoxygen injury[J]. CJCP, 2020, 22(5): 512-518.
Nabetani M, Shintaku H, Hamazaki T. Future perspectives of cell therapy for neonatal hypoxic-ischemic encephalopathy[J]. Pediatr Res, 2018, 83(1-2):356-363.
[2]
Yıldız EP, Ekici B, Tatlı B. Neonatal hypoxic ischemic encephalopathy:an update on disease pathogenesis and treatment[J]. Expert Rev Neurother, 2017, 17(5):449-459.
[3]
Hou Y, Qiao Y, Xiong M, et al. Hypothermia-rewarming:a double-edged sword?[J]. Med Hypotheses, 2019, 133:109387.
[4]
Zhao W, Qiu R, Li P, et al. PIM1:a promising target in patients with triple-negative breast cancer[J]. Med Oncol, 2017, 34(8):142.
[5]
Zhang M, Liu T, Sun H, et al. Pim1 supports human colorectal cancer growth during glucose deprivation by enhancing the Warburg effect[J]. Cancer Sci, 2018, 109(5):1468-1479.
[6]
Zou Y, Cao Y, Liu Y, et al. The role of dorsal root ganglia PIM1 in peripheral nerve injury-induced neuropathic pain[J]. Neurosci Lett, 2019, 709:134375.
[7]
Zhao B, Liu L, Mao J, et al. PIM1 mediates epithelial-mesenchymal transition by targeting Smads and c-Myc in the nucleus and potentiates clear-cell renal-cell carcinoma oncogenesis[J]. Cell Death Dis, 2018, 9(3):307.
[8]
Gao X, Liu X, Lu Y, et al. PIM1 is responsible for IL-6-induced breast cancer cell EMT and stemness via c-myc activation[J]. Breast Cancer, 2019, 26(5):663-671.
[9]
Remy J, Linder B, Weirauch U, et al. Inhibition of PIM1 blocks the autophagic flux to sensitize glioblastoma cells to ABT-737-induced apoptosis[J]. Biochim Biophys Acta Mol Cell Res, 2019, 1866(2):175-789.
[10]
Kuang X, Xiong J, Wang W, et al. PIM inhibitor SMI-4a induces cell apoptosis in B-cell acute lymphocytic leukemia cells via the HO-1-mediated JAK2/STAT3 pathway[J]. Life Sci, 2019, 219:248-256.
[11]
Herzog S, Fink MA, Weitmann K, et al. Pim1 kinase is upregulated in glioblastoma multiforme and mediates tumor cell survival[J]. Neuro Oncol, 2015, 17(2):223-242.
[12]
Weirauch U, Beckmann N, Thomas M, et al. Functional role and therapeutic potential of the pim-1 kinase in colon carcinoma[J]. Neoplasia, 2013, 15(7):783-794.
[13]
Zhang HH, Wang XT, Sun YH, et al. Pim1 overexpression prevents apoptosis in cardiomyocytes after exposure to hypoxia and oxidative stress via upregulating cell autophagy[J]. Cell Physiol Biochem, 2018, 49(6):2138-2150.
[14]
Liu N, Wang BJ, Broughton KM, et al. PIM1-minicircle as a therapeutic treatment for myocardial infarction[J]. PLoS One, 2017, 12(3):e0173963.
[15]
Kulandavelu S, Karantalis V, Fritsch J, et al. Pim1 kinase overexpression enhances ckit+ cardiac stem Ccell cardiac repair following myocardial infarction in swine[J]. J Am Coll Cardiol, 2016, 68(22):2454-2464.
[16]
Crowley LC, Waterhouse NJ. Detecting cleaved caspase-3 in apoptotic cells by flow cytometry[J]. Cold Spring Harb Protoc, 2016, 2016(11). DOI:10.1101/pdb.prot087312.
[17]
Zheng Z, Zhang L, Qu Y, et al. Mesenchymal stem cells protect against hypoxia-ischemia brain damage by enhancing autophagy through brain derived neurotrophic factor/mammalin target of rapamycin signaling pathway[J]. Stem Cells, 2018, 36(7):1109-1121.
Cao L, Wang F, Li S, et al. PIM1 kinase promotes cell proliferation, metastasis and tumor growth of lung adenocarcinoma by potentiating the c-MET signaling pathway[J]. Cancer Lett, 2019, 444:116-126.
[24]
Zhang X, Song M, Kundu JK, et al. PIM kinase as an executional target in cancer[J]. J Cancer Prev, 2018, 23(3):109-116.
[25]
Warfel NA, Sainz AG, Song JH, et al. PIM kinase inhibitors kill hypoxic tumor cells by reducing Nrf2 signaling and increasing reactive oxygen species[J]. Mol Cancer Ther, 2016, 15(7):1637-1647.
[26]
Xiang X, Yuan D, Liu Y, et al. PIM1 overexpression in T-cell lymphomas protects tumor cells from apoptosis and confers doxorubicin resistance by upregulating c-myc expression[J]. Acta Biochim Biophys Sin (Shanghai), 2018, 50(8):800-806.
[27]
Zhao F, Qu Y, Xiong T, et al. The neuroprotective role of TERT via an antiapoptotic mechanism in neonatal rats after hypoxia-ischemia brain injury[J]. Neurosci Lett, 2012, 515(1):39-43.
[28]
Li J, Qu Y, Chen D, et al. The neuroprotective role and mechanisms of TERT in neurons with oxygen-glucose deprivation[J]. Neuroscience, 2013, 252:346-358.
