Lin Yang1, Fei Xu2, Miao Zhang3, Xiao-Ying Shang4, Xin Xie2, Tao Fu2, Jian-Ping Li1, Hong-Lin Li5. 1. Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong 519041, China. 2. Department of Rehabilitation, Heilongjiang Provincial Hospital, Harbin, Heilongjiang 150036, China. 3. The Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150001, Heilongjiang, China. 4. Heilongjiang Provincial Hospital, Harbin, Heilongjiang 150036, China. 5. Department of Rehabilitation, The Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, No. 411, Guogeli Street, Nangang District, Harbin, Heilongjiang 150001, China. Electronic address: honglinfly@163.com.
Abstract
OBJECTIVE: To investigate the role of LncRNA MALAT-1 in hypoxia-induced cell injury. METHODS: Pheochromocytoma-12 (PC12) cells were divided into seven groups: Control group, Hypoxia group (Cells treated with CoCl2), MALAT-1 group (Hypoxic cells treated with MALAT-1), NC group (Hypoxic cells treated with empty plasmid), MALAT-1 siRNA group (Hypoxic cells treated with siRNA MALAT-1), SB203580 group (Hypoxic cells treated with p38MAPK inhibitor), and MALAT-1 + SB20358 group. The content of reactive oxygen species (ROS), malondialdehyde (MDA), super oxide dismutase (SOD) and lactate dehydrogenase (LDH) was determined. Cell viability was detected by MTT assay. Apoptotic cells were observed by Hoechst 33258 and TUNEL staining assay. Mitochondrial membrane potential (MMP) was measured using JC1 vital dye. RESULTS: The decreased cell viability and increased expressions of MALAT-1 and p-p38 were observed in hypoxic PC12 cells time-dependently (P < 0.05). Besides, hypoxic PC12 cells had an elevation in p-p38, ROS, MDA and LDH with the increased apoptotic cells, but a reduction in SOD and MMP, and these similar changes were more obvious in those hypoxic cells treated with MALAT-1 when compared with Controls (all P < 0.05). However, the hypoxic PC12 cells treated with SB203580 and MALAT-1 siRNA led to opposite results compared with MALAT-1 group (all P < 0.05). Importantly, SB203580 could reverse the function of MALAT-1 in aggravating the hypoxia injury of PC12 cells. CONCLUSION: MALAT-1 can promote the apoptosis and oxidative stress of PC12 cells by activating p38MAPK pathway, thus aggravating the damage of PC12 cells induced by chemical hypoxia.
OBJECTIVE: To investigate the role of LncRNA MALAT-1 in hypoxia-induced cell injury. METHODS:Pheochromocytoma-12 (PC12) cells were divided into seven groups: Control group, Hypoxia group (Cells treated with CoCl2), MALAT-1 group (Hypoxic cells treated with MALAT-1), NC group (Hypoxic cells treated with empty plasmid), MALAT-1 siRNA group (Hypoxic cells treated with siRNA MALAT-1), SB203580 group (Hypoxic cells treated with p38MAPK inhibitor), and MALAT-1 + SB20358 group. The content of reactive oxygen species (ROS), malondialdehyde (MDA), super oxide dismutase (SOD) and lactate dehydrogenase (LDH) was determined. Cell viability was detected by MTT assay. Apoptotic cells were observed by Hoechst 33258 and TUNEL staining assay. Mitochondrial membrane potential (MMP) was measured using JC1 vital dye. RESULTS: The decreased cell viability and increased expressions of MALAT-1 and p-p38 were observed in hypoxic PC12 cells time-dependently (P < 0.05). Besides, hypoxic PC12 cells had an elevation in p-p38, ROS, MDA and LDH with the increased apoptotic cells, but a reduction in SOD and MMP, and these similar changes were more obvious in those hypoxic cells treated with MALAT-1 when compared with Controls (all P < 0.05). However, the hypoxic PC12 cells treated with SB203580 and MALAT-1 siRNA led to opposite results compared with MALAT-1 group (all P < 0.05). Importantly, SB203580 could reverse the function of MALAT-1 in aggravating the hypoxia injury of PC12 cells. CONCLUSION: MALAT-1 can promote the apoptosis and oxidative stress of PC12 cells by activating p38MAPK pathway, thus aggravating the damage of PC12 cells induced by chemical hypoxia.