Spatiotemporal pattern of TRAF3 expression after rat spinal cord injury

Abstract

TNF receptor associated factor 3 (TRAF3), a member of the TRAF family of intracellular signaling proteins, can directly influence the phosphorylation status and activation of c-Jun N-terminal kinase, participating in CD40-induced apoptosis in carcinoma. However, its expression profile and function are still unclear in spinal cord injury (SCI). In this study, we performed an acute spinal cord contusion injury model in adult rats and detected the dynamic change patterns of TRAF3 expression in spinal cord. Western blot and immunohistochemistry revealed a striking upregulation of TRAF3 after SCI. Double immunofluorescence staining prompted that TRAF3 immunoreactivity was found in neurons rather than astrocytes. Moreover, co-localization of TRAF3/active caspase-3 was detected in neuronal nuclei. To further investigate the function of TRAF3, a neuronal cell line PC12 was employed to establish an apoptosis model in vitro. We analyzed the association of TRAF3 with active caspase-3 on PC12 cells by western blot and immunofluorescent labeling, which was parallel with the data in vivo. Additionally, knocking TRAF3 down with siRNA demonstrated the probable pro-apoptotic role of TRAF3 in the process of neuronal apoptosis. To summarize, we firstly uncover the temporal and spatial expression changes of TRAF3 in SCI. Our data suggest that TRAF3 might be implicated in central nervous system pathophysiology after SCI.

Role of TRAF3 in neurological and cardiovascular diseases: an overview of recent studies

“…In stroke, TRAF3 is associated with neuronal death (11,13), although other associations with other neurological conditions such as spinal cord injury (SCI) (15) and multiple sclerosis (17) have also been observed. In cardiovascular disease, an altered expression of TRAF3 is related with cardiac hypertrophy (10), atherosclerosis (18,19) and arterial injury (20).…”

“…In the first one, tissue detrition and necrosis occurs after the external injury. The second one involves an apoptotic process, oedema formation, electrolytic imbalance, ischaemia and inflammation, among other processes (15).…”

“…In accordance with these findings, TRAF3 affects JNK phosphorylation and activation to induce cellular apoptosis, a common phenotype after SCI. Whether this molecular mechanism can be generalised to other central nervous system injuries has yet to be evaluated (15).…”

“…TRAF3 is necessary for sustained B cells activation mediated by LMP1 through the downstream activation of JNK and NF-κβ (Table 1) (14). (13,15,16) NF-κβ, JNK and Rac-1 Stroke, SCI B cell activation (14) NF-κβ and JNK Multiple myeloma, EBV infection Microglia activation (17) MAPK and NF-κβ Multiple sclerosis Osteoclastogenesis (21) NF-κβ Osteoporosis Platelet aggregation (23) Vascular recurrence in patients treated with clopidogrel HIV, human immunodeficiency virus; SCI, spinal cord injury; EBV, Epstein-Barr virus. In addition, CD40, a TNF receptor, and LMP1 share TRAF3 for signal transduction in the activation of B cells (14).…”

“…In addition, CD40, a TNF receptor, and LMP1 share TRAF3 for signal transduction in the activation of B cells (14). Interestingly, mutations which inactivate TRAF3 are associated with B cell diseases, especially multiple myeloma (15).…”