Parascandolo Alessia, Laukkanen Mikko O
Center for Experimental Endocrinology and Oncology (IEOS), CNR, Via Pansini 5, 80131 Naples, Italy.
Antioxidants (Basel). 2021 Apr 21;10(5):635. doi: 10.3390/antiox10050635.
Superoxide dismutase (SOD) family isoenzymes, SOD1, SOD2, and SOD3, synthesize hydrogen peroxide (HO), which regulates the signal transduction. HO is a second messenger able to enter into the cells through aquaporin 3 cell membrane channels and to modify protein tyrosine phosphatase activity. SOD3 has been shown to activate signaling pathways in tissue injuries, inflammation, and cancer models. Similar to the HO response in the cells, the cellular response of SOD3 is dose-dependent; even a short supraphysiological concentration reduces the cell survival and activates the growth arrest and apoptotic signaling, whereas the physiological SOD3 levels support its growth and survival. In the current work, we studied the signaling networks stimulated by SOD3 overexpression demonstrating a high diversity in the activation of signaling cascades. The results obtained suggest that SOD3, although inducing cell growth and affecting various biological processes, does not cause detectable long-term DNA aberrations. Therefore, according to the present data, SOD3 is not a mutagen. Additionally, we compared SOD3-driven immortalized mouse embryonic fibroblasts to SV40 immortalized NIH3T3 cells, demonstrating a marked difference in the activation of cellular kinases. The data presented may contain important druggable targets to abrogate unwanted cell growth.
超氧化物歧化酶（SOD）家族同工酶SOD1、SOD2和SOD3可合成过氧化氢（HO），过氧化氢可调节信号转导。HO是一种第二信使，能够通过水通道蛋白3细胞膜通道进入细胞，并改变蛋白酪氨酸磷酸酶的活性。在组织损伤、炎症和癌症模型中，SOD3已被证明可激活信号通路。与细胞内的HO反应类似，SOD3的细胞反应也具有剂量依赖性；即使是短暂的超生理浓度也会降低细胞存活率，并激活生长停滞和凋亡信号，而生理水平的SOD3则支持细胞的生长和存活。在当前的研究中，我们研究了SOD3过表达所刺激的信号网络，结果表明信号级联激活具有高度多样性。所得结果表明，SOD3虽然能诱导细胞生长并影响各种生物学过程，但不会导致可检测到的长期DNA畸变。因此，根据目前的数据，SOD3不是诱变剂。此外，我们将SOD3驱动的永生化小鼠胚胎成纤维细胞与SV40永生化的NIH3T3细胞进行了比较，结果表明细胞激酶的激活存在显著差异。所呈现的数据可能包含消除不必要细胞生长的重要可药物作用靶点。
