Voltage-gated sodium channel 1.7 expression decreases in dorsal root ganglia in a spinal nerve ligation neuropathic pain model.

The role of the voltage-gated sodium channel 1.7 (Nav1.7) is unclear in models of neuropathic pain induced by nerve injury. In the present study, we measured expression levels of Nav1.7 in two distinct neuropathic pain models: spinal nerve ligation (SNL) and chronic constriction injury (CCI). In the SNL model, both mRNA and protein levels of Nav1.7 were markedly lower in the L5 dorsal root ganglia (DRG) but were significantly higher in the L4 DRG. Nav1.7 protein levels were notably higher in both L4 and L5 DRGs under CCI conditions. We found that excessive damage of L5 nerves such as SNL reduced expression levels of Nav1.7 in the injured L5 DRG and activated the adjacent uninjured DRG, resulting in Nav1.7 level increases in the adjacent L4 DRG. We confirmed again that Nav1.7 was closely related to neuropathic pain induced by nerve injury. More importantly, our results suggest that tracing the molecular changes exclusively in the L5 DRG in SNL model may not completely explain the pain mechanism; it is necessary to study the adjacent uninjured L4 DRG.

Expression of p53 isoforms in renal cell carcinoma.

BACKGROUND: Several isoforms of p53 have been reported, which may have varying functions and expressions. This study aimed to analyze the expression patterns of p53 isoforms in renal cell carcinoma (RCC) at the mRNA and protein levels and their associations with clinical and pathologic factors to explore the mechanism of p53 isoforms' activity in RCC. METHODS: The specimens of tumours (T) and clinically normal tissues (N) adjacent to them were collected from 41 patients with RCC. mRNA expression levels of p53 isoforms were detected using RT-PCR followed by nested PCR. Protein expression levels were detected using immunohistochemisty and Western blotting with the anti-p53 antibodies DO-1 and DO-12. The data were analyzed with clinicopathological features by chi(2) test or Fisher's exact test. RESULTS: p53 mRNA was expressed in all tumours and matched clinically normal tissue adjacent to the tumour. All six isoforms could be detected in tumour and normal tissues, with the exception of the Delta133p53beta isoform, which was not detected in the normal tissue. Of the six isoforms, p53beta mRNA was significantly overexpressed in tumour samples (P < 0.001), and correlated with tumour stage. Nested PCR results consistently indicated the presence of p53gamma (19T/22N), Delta133p53 (33T/26N), Delta133p53beta (2T/0N), and Delta133p53gamma (13T/9N). Immunohistochemical analysis showed that p53 was expressed only in tumour tissues and correlated with tumour stage and grade. The results of Western blotting analysis were consistent with these findings. CONCLUSIONS: Although all six isoforms are present in RCC, their function in tumour development or progression might be different. Our findings suggest that p53beta might play an important role in the formation of RCC and it might be used as a new predictor and therapeutic target for RCC.