Siddiqui Sharif Hasan, Khan Mousumee, Park Jinryong, Lee Jeongeun, Choe Hosung, Shim Kwanseob, Kang Darae
Center for Musculoskeletal Research, School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, NY, United States.
Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States.
Front Vet Sci. 2023 Feb 24;10:985040. doi: 10.3389/fvets.2023.985040. eCollection 2023.
Heat stress inhibits cellular proliferation and differentiation through the production of reactive oxygen species. Under stress conditions, antioxidant drugs promote stable cellular function by reducing the stress level. We sought to demonstrate 9-mer disulfide dimer peptide (COPA3) supplementation stabilizes fibroblast proliferation and differentiation even under heat stress conditions. In our study, fibroblasts were assigned to two different groups based on the temperature, like 38°C group presented as Control - and 43°C group presented as Heat Stress-. Each group was subdivided into two groups depending upon COPA3 treatment, like 38°C + COPA3 group symbolized Control+ and the 43°C + COPA3 group symbolized as Heat Stress+. Heat stress was observed to decrease the fibroblast viability and function and resulted in alterations in the fibroblast shape and cytoskeleton structure. In contrast, COPA3 stabilized the fibroblast viability, shape, and function. Moreover, heat stress and COPA3 were found to have opposite actions with respect to energy production, which facilitates the stabilization of cellular functions by increasing the heat tolerance capacity. The gene expression levels of antioxidant and heat shock proteins were higher after heat stress. Additionally, heat stress promotes the mitogen-activated protein kinase/ extracellular signal-regulated kinase-nuclear factor erythroid 2-related factor 2 (MAPK/ERK-Nrf2). COPA3 maintained the MAPK/ERK-Nrf2 gene expressions that promote stable fibroblast proliferation, and differentiation as well as suppress apoptosis. These findings suggest that COPA3 supplementation increases the heat tolerance capacity, viability, and functional activity of fibroblasts.
热应激通过产生活性氧抑制细胞增殖和分化。在应激条件下,抗氧化药物通过降低应激水平促进细胞功能稳定。我们试图证明,即使在热应激条件下,补充9聚体二硫键二聚体肽(COPA3)也能稳定成纤维细胞的增殖和分化。在我们的研究中,根据温度将成纤维细胞分为两组,如38°C组为对照组,43°C组为热应激组。每组根据COPA3处理再细分为两组,如38°C + COPA3组表示为对照组+,43°C + COPA3组表示为热应激+组。观察到热应激会降低成纤维细胞的活力和功能,并导致成纤维细胞形状和细胞骨架结构的改变。相比之下,COPA3能稳定成纤维细胞的活力、形状和功能。此外,发现热应激和COPA3在能量产生方面具有相反的作用,这通过提高耐热能力促进细胞功能的稳定。热应激后抗氧化蛋白和热休克蛋白的基因表达水平更高。此外,热应激促进丝裂原活化蛋白激酶/细胞外信号调节激酶-核因子红细胞2相关因子2(MAPK/ERK-Nrf2)。COPA3维持促进成纤维细胞稳定增殖、分化以及抑制细胞凋亡的MAPK/ERK-Nrf2基因表达。这些发现表明,补充COPA3可提高成纤维细胞的耐热能力、活力和功能活性。