Institute of Cell Biophysics, FSC PBCRAS, Institutskaya str., 3, Pushchino, Moscow region, 142290, Russia.
Cell Physiol Biochem. 2024 Sep 23;58(5):527-537. doi: 10.33594/000000729.
BACKGROUND/AIMS: There are evidences that a decrease in the functional activity of pancreatic β-cells under type 2 diabetes conditions may be associated with their senescence, therefore, senotherapy may be a prospective strategy for the diabetes treatment.
The senotherapeutic potential of peroxiredoxin 6 (PRDX6) was studied in RIN-m5F pancreatic β-cells with streptozotocin-induced senescence by measuring markers, associated with senescence.
Exposure to streptozotocin (STZ) resulted in the senescence of the β-cells. The addition of PRDX6 to the culture medium of RIN-m5F β-cells before treatment with STZ decreased the levels of the following senescence markers: the percentage of SA-β-Gal-positive cells, the phosphorylation of histone H2AX and p21 proteins, and the secretion of the proinflammatory cytokine IL-6 but not the anti-inflammatory cytokine IL-10. These effects were accompanied by a decrease in the production of reactive oxygen species (ROS) and the restoration of impaired NF-κB activation. In addition, PRDX6 altered the production of the heat shock protein HSP90: the production of the constitutive form of HSP90-beta decreased, while the level of inducible HSP90-alpha increased.
PRDX6 prevented the senescence of RIN-m5F cells in response to the DNA damage-inducing agent streptozotocin, indicating a potential protective role of PRDX6 in type 2 diabetes mellitus.
背景/目的：有证据表明，2 型糖尿病条件下胰腺 β 细胞功能活性的降低可能与其衰老有关，因此，衰老治疗可能是糖尿病治疗的一种有前景的策略。
通过测量与衰老相关的标志物，研究过氧化物还原酶 6（PRDX6）在链脲佐菌素诱导的 RIN-m5F 胰腺 β 细胞衰老中的衰老治疗潜力。
链脲佐菌素（STZ）的暴露导致 β 细胞衰老。在 STZ 处理前将 PRDX6 添加到 RIN-m5F β 细胞的培养基中，降低了以下衰老标志物的水平：SA-β-Gal 阳性细胞的百分比、组蛋白 H2AX 和 p21 蛋白的磷酸化以及促炎细胞因子 IL-6 的分泌，但不影响抗炎细胞因子 IL-10。这些作用伴随着活性氧（ROS）的产生减少和受损的 NF-κB 激活的恢复。此外，PRDX6 改变了热休克蛋白 HSP90 的产生：组成型 HSP90-β 的产生减少，而诱导型 HSP90-α 的水平增加。
PRDX6 可预防 RIN-m5F 细胞对 DNA 损伤诱导剂链脲佐菌素的衰老，表明 PRDX6 在 2 型糖尿病中的潜在保护作用。
Zotero 插件