Work

B-cell lymphoma-extra large expression correlated with protein kinase RNA-like ER kinase and ubiquitination signals in the type 1 diabetes mouse model

Year: 2025

Type: article

Abstract: Introduction: Diabetes mellitus with pain sensation is referred to as diabetic painful neuropathy (DN). DN development results from endoplasmic reticulum (ER) stress, including the upregulation of ER stress signaling–related molecules and autophagy. B-cell lymphoma-extra large (Bcl- XL ), a protein of the antiapoptotic Bcl2 family, exhibits neuroprotective efficacy and expression profiles similar to those of protein kinase RNA-like ER kinase (PERK) in DN. Objectives: To investigate the roles of Bcl- XL in type 1 diabetes mellitus (T1DM). Methods: This report used a single dose of streptozotocin (200 mg/kg) to establish a mouse model of T1DM, and to assay the changes in the expression profile of Bcl- XL and ER stress-related signal molecules with the dorsal root ganglia tissues. Results: This study discovered the coexpression of Bcl- XL upregulation and PERK, a downstream mediator of ER stress (M1 Manders coefficients: 0.48–0.61, M2 Manders coefficients: 0.41–0.61). PERK phosphorylated eukaryotic initiation factor 2α (p-eIF2α) in the same sensory nociceptors (M1 Manders coefficients: 0.94–0.98, and M2 Manders coefficients: 0.97–0.98). This eIF2α upregulation was inversely correlated with thermal latencies ( r = –0.89, p < 0.0001) and mechanical thresholds ( r = –0.75, p < 0.0001). In addition to PERK upregulation, ubiquitin D (UBD), a key molecule in ubiquitination signaling, was upregulated and inversely correlated with neuropathic pain in DN. Conclusions: This study uncovers a new neuropathology underlying T1DM-associated DN: Bcl- XL activation associates PERK and ubiquitination marker upregulation in sensory neurons. Bcl- XL inactivation in nociceptors might be a potential target for relieving neuropathic pain of T1DM.

Source: PAIN Reports

DOI: 10.1097/pr9.0000000000001356

Authors: Yu-Yu Kan, Ying-Shuang Chang, Tzu-Ning Chao, Yu-Lin Hsieh

Institutions: National Sun Yat-sen University, Kaohsiung Medical University, Kaohsiung Medical University Chung-Ho Memorial Hospital

Language: English

Topic: Endoplasmic Reticulum Stress and Disease

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,500