Dataset Information

Overexpression of lncRNA TCTN2 protects neurons from apoptosis by enhancing cell autophagy in spinal cord injury.

ABSTRACT: Neuronal apoptosis is the main pathological feature of spinal cord injury (SCI), while autophagy contributes to ameliorating neuronal damage via inhibition of apoptosis. Here, we investigated the role of tectonic family member 2 (TCTN2) long non-coding RNA on apoptosis and autophagy in SCI. TCTN2 was down-regulated in the spinal cord tissues of a rat model of SCI and in oxygen-glucose deprivation-induced hypoxic SY-SH-5Y cells, while microRNA-216b (miR-216b) was up-regulated. Overexpression of TCTN2 reduced neuron apoptosis by inducing autophagy, and TCTN2 was observed to negatively regulate miR-216b. Furthermore, TCTN2 promoted autophagy to repress apoptosis through the miR-216b-Beclin-1 pathway, and overexpression of TCTN2 improved neurological function in the SCI rat model. In summary, our data suggest that TCTN2 enhances autophagy by targeting the miR-216b-Beclin-1 pathway, thereby ameliorating neuronal apoptosis and relieving spinal cord injury.

SUBMITTER: Ren XD

PROVIDER: S-EPMC6609579 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Overexpression of lncRNA TCTN2 protects neurons from apoptosis by enhancing cell autophagy in spinal cord injury.

Ren Xiao-Dong XD Wan Chun-Xiao CX Niu Ya-Li YL

FEBS open bio 20190604 7

Neuronal apoptosis is the main pathological feature of spinal cord injury (SCI), while autophagy contributes to ameliorating neuronal damage via inhibition of apoptosis. Here, we investigated the role of tectonic family member 2 (TCTN2) long non-coding RNA on apoptosis and autophagy in SCI. TCTN2 was down-regulated in the spinal cord tissues of a rat model of SCI and in oxygen-glucose deprivation-induced hypoxic SY-SH-5Y cells, while microRNA-216b (miR-216b) was up-regulated. Overexpression of T ...[more]

PMID: 31050183

Similar Datasets

Project description:BackgroundThere is emerging evidence that astaxanthin plays a significant role in protecting neuro-cells from apoptosis after central nervous system injury. Our study examined the effects of astaxanthin on neuro-cell apoptosis after spinal cord injury.MethodsOne hundred and forty-four healthy adult Sprague-Dawley rats were randomly divided into the experimental group, control group, and sham operation group (n=48). Spinal cord injury was induced using the modified Allen method in the control group and the experimental group; while in the sham operation group, the lamina was removed without spinal cord injury. The rats in the experimental group were given astaxanthin (75 mg/kg) by gavage immediately after the operation, and in the other groups were given the same amount of olive oil. Motor function was assessed by blood-brain barrier (BBB) scores. The malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) at 24 h was determined after the operation. The apoptosis index (AI) was determined at 6, 24, and 48 h after the operation. At 48 h after the operation, we calculated the water content of the spinal cord, the lesion ratio of the spinal cord, the ultrastructure of the spinal cord, and the ultrastructure score.ResultsThe BBB scores of the control and experimental groups were significantly lower than the sham operation group at each postoperative time (P<0.05), and the BBB score of the experimental group was significantly higher than the control group at 1-4 weeks postoperatively (P<0.05). At 24 hours postoperatively, MDA content was highest in the control group and lowest in the sham operation group, while SOD activity was highest in the sham operation group and lowest in the control group (P<0.05). At each time point postoperatively, the sham operation group had the lowest AI and the control group had the highest AI (P<0.05). At 48 h after the operation, the water content and the lesion ratio of the spinal cord, and the ultrastructure score were the lowest in the sham operation group and the highest in the control group (P<0.05).ConclusionsAstaxanthin significantly improved the motor function of rats with spinal cord injury.

Project description:Previously, we reported that RhoA knockdown by morpholino antisense oligonucleotides (MOs), and enzymatic digestion of chondroitin sulfate proteoglycans (CSPGs) at the site of injury with chondroitinase ABC (ChABC), each can reduce retrograde neuronal apoptosis after spinal cord transection in the lamprey. To elucidate the mechanisms in neuronal survival and axon regeneration, we have investigated whether these two effects are additive in vivo. We used lampreys as a spinal cord injury model. MOs were used to knockdown RhoA and Chondroitinase ABC (ChABC) was used to digest CSPGs in vivo. Retrograde labeling, fluorochrome-labeled inhibitor of caspase activity (FLICA), immunohistochemistry, and western blots were performed to assess axonal regeneration, neuronal apoptotic signaling and Akt activation. Four treatment combinations were evaluated at 2-, 4-, and 10-weeks post-transection: (1) Control MO plus enzyme buffer (Ctrl); (2) control MO plus ChABC; (3) RhoA MO plus enzyme buffer (RhoA MO); and (4) RhoA MO plus ChABC (RhoA MO + ChABC). Consistent with our previous findings, at 4-weeks post-transection, there was less caspase activation in the ChABC and RhoA MO groups than in the Ctrl group. Moreover, the RhoA MO plus ChABC group had the best protective effect on identified reticulospinal (RS) neurons among the four treatment combinations. At 2 weeks post-transection, when axons have retracted maximally in the rostral stump and are beginning to regenerate back toward the lesion, the axon tips in the three treatment groups each were closer to the transection than those in the Ctr MO plus enzyme buffer group. Long-term axon regeneration also was evaluated for the large, individually identified RS neurons at 10 weeks post-transection by retrograde labeling. The percent regenerated axons in the RhoA MO plus ChABC group was greater than that in any of the other groups. Akt phosphorylation levels at threonine 308 was quantified in the identified RS neurons by western blots and immunofluorescence. The RhoA MO plus ChABC treatment enhanced pAkt-308 phosphorylation more than any of the other treatment groups. Although some of the effects of CSPGs are mediated through RhoA activation, some growth-inhibiting mechanisms of RhoA and CSPGs are independent of each other, so combinatorial therapies may be warranted.

Project description:BackgroundSpinal cord injury (SCI) is a neurological disease associated with a high disability rate. Low-dose lipopolysaccharide (LPS) has been reported to activate cross-immune tolerance and alleviate the effects of various traumatic stimuli. The present study aimed to explore the effect of LPS on SCI and the potential molecular mechanism.MethodsMale Sprague-Dawley (SD) rats were used to established an in vivo SCI model and were intraperitoneally injected with lentivirus particles encoding a MALAT1 small interfering RNA (siRNA) on day 10 prior to SCI and with 0.2 mg/kg LPS 72 h prior to SCI. Basso, Beattie, and Bresnahan (BBB) scoring; HE staining; and TUNEL assay were used to assess neurological function and pathophysiological changes. Western blot and immunohistochemistry (IHC) were used to detect cell autophagy and Nrf2 nuclear translocation. PC12 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to establish an in vitro SCI model. In vitro SCI model cells were pretreated with LPS and transfected with siMALAT1 or MALAT1 overexpression plasmid aimed at knocking down MALAT1 or overexpressing MALAT1. The cell counting kit-8 (CCK-8) assay was used to measure the toxicity of LPS towards PC12 cells. Flow cytometry and immunofluorescence analysis were performed to investigate cell apoptosis and Nrf2 nuclear translocation.ResultsSCI rats preconditioned with low-dose LPS had higher BBB scores, reduced SCI injury, increased MALAT1 expression and activated autophagy and Nrf2 nuclear translocation in the in vivo SCI model. In the in vitro SCI model, low-dose LPS treatment suppressed the apoptotic ratio of PC12 cells, increased MALAT1 expression, activated autophagy, and promoted Nrf2 nuclear translocation. Silencing MALAT1 exacerbated OGD/R injury in vitro and weakened the protective effect of low-dose LPS. Overexpression of MALAT1 inhibits OGD/R-induced apoptosis by inducing autophagy and promoting Nrf2 nuclear translocation. This was also been confirmed in animal experiments, silencing MALAT1 blocked the promotion of Nrf2 by low-dose LPS and the alleviated of SCI apoptosis.ConclusionsLow-dose LPS exhibited a protective role on SCI by activating autophagy and suppressing nerve cell apoptosis via the lncRNA MALAT1/Nrf2 axis.

Project description:Ozone therapy can relieve multiple types of pain but exhibits potential neurotoxicity, the mechanism of which is unclear. The present study aimed to identify the role of nuclear factor (erythroid‑derived‑2)‑related 2 (NRF2) in preventing spinal cord injury caused by ozone overdose. Primary neuronal cells were extracted from newborn Wistar rats and authenticated by immunofluorescence using anti‑microtubule‑associated protein 2 as a cell type‑specific marker. Cell viability assay with different ozone concentrations (0, 10, 20, 30 and 40 µg/ml) was used to determine the concentration that caused primary neuron injury; 30 min of 40 µg/ml ozone therapy notably decreased cell viability to 71%. In order to test the effects of ozone, the cells were divided into five treatment groups [0‑, 30‑ and 40 µg/ml ozone, tert‑butylhydroquinone (tBHQ) + 40 µg/ml ozone (T40) and tBHQ (T0)]. Cells in the T40 and T0 groups received 40 µmol/l tBHQ on the fifth day of SCN cultivation. Reverse transcription‑quantitative PCR and western blotting showed that protein expression levels of heme oxygenase‑1 (HO‑1) and mRNA expression levels of HO‑1 and NRF2 were decreased. NRF2, ubiquitin‑binding protein p62 and microtubule‑associated proteins 1A/1B light chain 3B expression levels were decreased following treatment with 40 µg/ml ozone. Immunofluorescence showed that NRF2 nuclear expression levels also decreased following 40 µg/ml ozone treatment. However, cells in the T40 group did not display decreased NRF2 nuclear expression levels. Normal/Apoptotic/Necrotic Cell Detection kit revealed that necrosis rate increased following treatment with 40 µg/ml ozone; however, the T40 group did not exhibit this increased necrosis. At 40 µg/ml, ozone increased spinal cord neuron (SCN) death in vitro. Moreover, treatment with 40 µg/ml ozone damaged SCNs. The p62/NRF2/antioxidant response element pathway prevented such injury. tBHQ activated this pathway, upregulated autophagy and increased local nuclear NRF2 concentration, thus enhancing the antioxidant system to protect SCNs from injury caused by high concentrations of ozone.

Dataset Information

Overexpression of lncRNA TCTN2 protects neurons from apoptosis by enhancing cell autophagy in spinal cord injury.

Publications

Overexpression of lncRNA TCTN2 protects neurons from apoptosis by enhancing cell autophagy in spinal cord injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets