Developmental endothelial locus-1 enhances ER calmodulin expression, mitigates ER stress, suppresses inflammation, and attenuates neuronal apoptosis

doi:10.5246/jcps.2024.09.059

Abstract

Abstract:

This study aimed to investigate the impact of developmental endothelial locus-1 (Del-1) on sarcoplasmic reticulum Ca²⁺ ATPase 2 (SERCA2) and its potential effects on spinal cord injury (SCI). A total of 48 mice were randomly assigned to the sham group, SCI group, and SCI + CE group. Each group was further divided into two subgroups. The Del treatment subgroup received tail-vein injections of Del-1 (1 μg/d) for a consecutive week, while the other group was injected with an equivalent volume of normal saline. After 1 week of experimentation, the mice were euthanized, and the spinal cord was extracted for further analysis. Initially, the impact of Del-1 on SERCA2 in the spinal cord was assessed using western blotting analysis. Subsequently, the effects of Del-1 on stress, inflammation, and apoptosis in the endoplasmic reticulum (ER) of SCI mice were analyzed through Western blotting analysis and fluorescent TUNEL. Finally, the study utilized Western blotting analysis and fluorescent TUNEL analysis to examine the consequences of Del-1 blocking SERCA2 on ER stress, inflammation, and apoptosis in mice. The results revealed that Del-1 treatment significantly increased the expression of SERCA2 in the spinal cord (P < 0.01) and mitigated SCI-induced ER stress, inflammation, and neuronal apoptosis (P < 0.01). Blocking SERCA2 expression in the spinal cord of SCI mice promoted ER stress, inflammatory response, and neuronal cell apoptosis (P < 0.01). However, Del-1 treatment did not alleviate the effects of blocking SERCA2 on ER stress, inflammatory response, and neuronal cell apoptosis (P > 0.05). In conclusion, this study proposed that Del-1 could reduce ER stress, inflammatory response, and nerve cell apoptosis in spinal cord injury by enhancing the expression of SERCA2.

Key words: SCI, Del-1, SERCA2, Inflammation, Apoptosis

Supporting:

Hao Wang, Kangxue Chen, Yuyan Zhang, Kuijun Jiang, Zhonglei Sun. Developmental endothelial locus-1 enhances ER calmodulin expression, mitigates ER stress, suppresses inflammation, and attenuates neuronal apoptosis[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(9): 795-804.

Figures/Tables 6

Table 1. The relative content of SERCA2 protein in the spinal cord of mice in each group (s, x ± s, n = 8).

Table 2. Relative contents of related proteins in each group of mice (s, x ± s, n = 8).

Table 3. Relative contents of related proteins in each group of mice (s, x ± s, n = 8).

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