Neuromuscular Studies Lab (NeSt Lab), Instituto de Anatomía, Histología y Patología, Facultad de Medicina, Universidad Austral de Chile, Valdivia, 5110566, Chile.
Facultad de Ciencias Veterinarias, Universidad de Concepción, Chillán, 3812120, Chile.
Biol Res. 2024 Nov 6;57(1):79. doi: 10.1186/s40659-024-00554-6.
Vitamin C plays key roles in cellular homeostasis, functioning as a potent antioxidant and a positive regulator of cell differentiation. In skeletal muscle, the vitamin C/sodium co-transporter SVCT2 is preferentially expressed in oxidative slow fibers. SVCT2 is up-regulated during the early fusion of primary myoblasts and decreases during initial myotube growth, indicating the relevance of vitamin C uptake via SVCT2 for early skeletal muscle differentiation and fiber-type definition. However, our understanding of SVCT2 expression and function in adult skeletal muscles is still limited.
In this study, we demonstrate that SVCT2 exhibits an intracellular distribution in chicken slow skeletal muscles, following a highly organized striated pattern. A similar distribution was observed in human muscle samples, chicken cultured myotubes, and isolated mouse myofibers. Immunohistochemical analyses, combined with biochemical cell fractionation experiments, reveal a strong co-localization of SVCT2 with intracellular detergent-soluble membrane fractions at the central sarcomeric M-band, where it co-solubilizes with sarcoplasmic reticulum proteins. Remarkably, electrical stimulation of cultured myofibers induces the redistribution of SVCT2 into a vesicular pattern.
Our results provide novel insights into the dynamic roles of SVCT2 in different intracellular compartments in response to functional demands.
维生素 C 在细胞内稳态中发挥着关键作用，作为一种有效的抗氧化剂和细胞分化的正调节剂。在骨骼肌中，维生素 C/钠协同转运体 SVCT2 优先表达于氧化型慢肌纤维。SVCT2 在原代成肌细胞早期融合时上调，在初始肌管生长时下调，表明通过 SVCT2 摄取维生素 C 对早期骨骼肌分化和纤维型定义具有重要意义。然而，我们对成年骨骼肌中 SVCT2 的表达和功能的理解仍然有限。
在这项研究中，我们证明 SVCT2 在鸡慢肌中呈现一种高度有组织的条纹状的细胞内分布模式。在人类肌肉样本、鸡培养的肌管和分离的小鼠肌纤维中也观察到类似的分布。免疫组织化学分析结合生化细胞分级实验表明，SVCT2 与中央肌节 M 带的胞内去垢剂可溶性膜部分强烈共定位，在该处与肌浆网蛋白共溶解。值得注意的是，对培养的肌纤维进行电刺激可诱导 SVCT2 重新分布为囊泡样模式。
我们的研究结果提供了新的见解，即 SVCT2 在不同的细胞内隔室中根据功能需求发挥动态作用。
