Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.99.3 (PRE)
 1,923 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

No study has been conducted to examine the interactions of sigma-1 receptor (Sigma-1R) and high mobility group box 1 protein (HMGB1) in the development of diabetic peripheral neuropathy. Thus, we examined the effects of streptozotocin (STZ) treatment on expression of HMGB1 in subcellular levels in the dorsal root ganglion (DRG) in both wild-type and Sigma-1R-/- mice and evaluated the effects of repeated intrathecal administrations of selective Sigma-1R antagonists BD1047, agonist PRE-084, or HMGB1 inhibitor glycyrrhizin on peripheral neuropathy in wild-type mice. We found that STZ-induced tactile allodynia and thermal hyperalgesia was associated with increased total HMGB1 expression in DRG. STZ treatment promoted the distribution of HMGB1 into cytoplasm. Furthermore, STZ induced modest peripheral neuropathy and did not alter HMGB1 levels in DRG or the distribution of either cytoplasmic or nuclear HMGB1 in Sigma-1R-/- mice compared to sham control mice. Additionally, repeated stimulation of Sigma-1R in the spinal cord induced tactile allodynia and thermal hyperalgesia at 1 week. This phenomenon was associated with increased cytoplasmic HMGB1 translocation and HMGB1 expression in DRG. Finally, we found that repeated blockade of either Sigma-1R or HMGB1 in the spinal cord after STZ treatment prevent the development of tactile allodynia and thermal hyperalgesia at 1 week. These effects were associated with decreased cytoplasmic HMGB1 translocation and HMGB1 expression in DRG. Taken together, our results suggest that Sigma-1R-mediated enhancement of HMGB1 expression in the DRG is critical for the development of peripheral neuropathy in type 1 diabetes.
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PMID:Sigma 1 receptor mediated HMGB1 expression in spinal cord is involved in the development of diabetic neuropathic pain. 2942 43