College of Pharmacy, Nova Southeastern University, Fort Lauderdale, Florida, USA.
College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Endocr Regul. 2020 Jul 1;54(3):172-182. doi: 10.2478/enr-2020-0020.
Oxytocin (OXT) participates in various physiological functions ranging from reproduction to social and non-social behaviors. Recent studies indicate that OXT affects cell growth and metabolism. Here we characterized the growth stimulating and antioxidant actions of OXT and of OXT receptors (OXTR) in a glial cell-line (U-87MG).
We developed an OXTR-knockdown cell-line (U-87MG KD) to establish the receptor specificity of OXT's actions, and the impact of lacking OXTR on growth and survival in glial cells. The role Extracellular-Signal Regulated Kinases (ERK1/2) on glial cell protection against consequences of oxidative stress, and cell proliferation was investigated.
In U-87MG cells, OXT stimulated cell proliferation and increased ERK1/2 phosphorylation. The specific ERK1/2 inhibitor, PD098059, produced marked inhibition of cell proliferation, and antagonized the stimulating effect of OXT on ERK1/2 phosphorylation and on cell proliferation. Slower growth rates and lower levels of phosphorylated ERK1/2 were observed in OXTR-knockdown cells and in U-87MG cells treated with an OXTR antagonist (L-371,257). In addition to increasing cell proliferation, OXT significantly blunted the rise in reactive oxygen species induced by H2O2, and antagonized the reductions in cell viability induced by H2O2 and camptothecin. The cell protective and antioxidant actions of OXT in U-87MG cells were not observed in the OXTR-knockdown cells.
OXT stimulates the growth of astrocyte-like cells acting on OXTR via ERK1/2 phosphorylation. The protection against apoptosis and the antioxidant capacity of OXT may contribute to the observed increase in cell proliferation. Oxytocin and OXTR appear to be fundamental for cell growth and viability of glial cells.
催产素（OXT）参与从生殖到社会和非社会行为等各种生理功能。最近的研究表明，OXT 影响细胞生长和代谢。在这里，我们描述了 OXT 和 OXT 受体（OXTR）在神经胶质细胞系（U-87MG）中的生长刺激和抗氧化作用。
我们开发了一种 OXTR 敲低细胞系（U-87MG KD），以确定 OXT 作用的受体特异性，以及缺乏 OXTR 对神经胶质细胞生长和存活的影响。研究了细胞外信号调节激酶（ERK1/2）在保护神经胶质细胞免受氧化应激后果和细胞增殖中的作用。
在 U-87MG 细胞中，OXT 刺激细胞增殖并增加 ERK1/2 磷酸化。特异性 ERK1/2 抑制剂 PD098059 对细胞增殖产生明显抑制，并拮抗 OXT 对 ERK1/2 磷酸化和细胞增殖的刺激作用。在 OXTR 敲低细胞和用 OXTR 拮抗剂（L-371,257）处理的 U-87MG 细胞中，观察到生长速度较慢和磷酸化 ERK1/2 水平较低。除了增加细胞增殖外，OXT 还显著减弱了 H2O2 诱导的活性氧增加，并拮抗了 H2O2 和喜树碱诱导的细胞活力降低。在 U-87MG 细胞中，OXT 的细胞保护和抗氧化作用在 OXTR 敲低细胞中未观察到。
OXT 通过 ERK1/2 磷酸化作用于 OXTR 刺激星形胶质样细胞的生长。OXT 的抗凋亡和抗氧化能力可能有助于观察到的细胞增殖增加。催产素和 OXTR 似乎对神经胶质细胞的生长和活力至关重要。
