To explore the role of Na+/H+ exchanger-1 (NHE-1 ) gene expression in intracellular PH (pHi) regulation and the modulation of apoptosis of human lung cancer cells. Methods: After the human lung cell line A549 cells we...To explore the role of Na+/H+ exchanger-1 (NHE-1 ) gene expression in intracellular PH (pHi) regulation and the modulation of apoptosis of human lung cancer cells. Methods: After the human lung cell line A549 cells were incubated with a 21-mer antisense phosphorothioate oligodeoxynucleotide (ASODN) complementary to NHE-1 gene, the acidification effects of AS-ODN on A549 cells was investigated with fluorescent probe labeling and the apoptotic rate of these cells determined with in situ cell apoptosis detection. Results: Intracellular acidification (pHi from 7. 12 to 6. 55) and cell apoptosis of A549 cells induced by AS-ODN were correlated to dose of the agent. The apoptotic rate was found to be 30. 1 %, 91. 2% and 99. 6% respectively at the end of incubation time of 24, 48 and 72 h with 20μmol/L AS--ODN. Under the electron microscope, morphological changes of cell apoptosis were seen. Conclusion: Intracellular acidification (pHi<6. 55) can trigger apoptosis of human lung cancer cells and NHE-1 gene expression plays an important role in the regulation of apoptosis of the human lung cancer cells through preventing intracellular acidification.展开更多
Astrocyte elevated gene-1 (AEG-1) was cloned as an human immunodeficiency virus -1-inducible and tumor necrosis factor-α-inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization app...Astrocyte elevated gene-1 (AEG-1) was cloned as an human immunodeficiency virus -1-inducible and tumor necrosis factor-α-inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization approach. AEG-1 down-regulates the expression of the glutamate transporter EAAT2,thus,it is implicated in glutamate-induced excitotoxic damage to neurons as evident in HIV-associated neurodegeneration. Meanwhile,AEG-1 expression is elevated in subsets of breast cancer,prostatic cancer,glioblastoma multiforme and melanoma cells,having a dual specificity phosphatase activity. Overexpression of AEG-1 increases and siRNA inhibition of AEG-1 decreases migration and invasion of human glioma cells,respectively. Recent observations indicate that AEG-1 exerts its effects by activating the nuclear factor kappa B (NF-κB) pathway and AEG-1 is a downstream target of Ha-ras and plays an important role in Ha-ras-mediated tumorigenesis. These findings are intensifying interest in AEG-1 as a crucial regulator of tumor progression and metastasis and as a potential mediator of neurodegeneration.展开更多
基金supported by grant from the scientif ic fund of the Ministry of Personnel for returned overseas expert (2006)Natural Science Foundation Project of CQ CSTC (to Mingjian GE)(CSTC, No.2008BB5210)
文摘To explore the role of Na+/H+ exchanger-1 (NHE-1 ) gene expression in intracellular PH (pHi) regulation and the modulation of apoptosis of human lung cancer cells. Methods: After the human lung cell line A549 cells were incubated with a 21-mer antisense phosphorothioate oligodeoxynucleotide (ASODN) complementary to NHE-1 gene, the acidification effects of AS-ODN on A549 cells was investigated with fluorescent probe labeling and the apoptotic rate of these cells determined with in situ cell apoptosis detection. Results: Intracellular acidification (pHi from 7. 12 to 6. 55) and cell apoptosis of A549 cells induced by AS-ODN were correlated to dose of the agent. The apoptotic rate was found to be 30. 1 %, 91. 2% and 99. 6% respectively at the end of incubation time of 24, 48 and 72 h with 20μmol/L AS--ODN. Under the electron microscope, morphological changes of cell apoptosis were seen. Conclusion: Intracellular acidification (pHi<6. 55) can trigger apoptosis of human lung cancer cells and NHE-1 gene expression plays an important role in the regulation of apoptosis of the human lung cancer cells through preventing intracellular acidification.
文摘Astrocyte elevated gene-1 (AEG-1) was cloned as an human immunodeficiency virus -1-inducible and tumor necrosis factor-α-inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization approach. AEG-1 down-regulates the expression of the glutamate transporter EAAT2,thus,it is implicated in glutamate-induced excitotoxic damage to neurons as evident in HIV-associated neurodegeneration. Meanwhile,AEG-1 expression is elevated in subsets of breast cancer,prostatic cancer,glioblastoma multiforme and melanoma cells,having a dual specificity phosphatase activity. Overexpression of AEG-1 increases and siRNA inhibition of AEG-1 decreases migration and invasion of human glioma cells,respectively. Recent observations indicate that AEG-1 exerts its effects by activating the nuclear factor kappa B (NF-κB) pathway and AEG-1 is a downstream target of Ha-ras and plays an important role in Ha-ras-mediated tumorigenesis. These findings are intensifying interest in AEG-1 as a crucial regulator of tumor progression and metastasis and as a potential mediator of neurodegeneration.
