Cystine and tyrosine feed reduces oxidative and ER stress in CHO cells
Yusuke Shibafuji, Nobuyoshi Nagao, Masafumi Yohda
Abstract
Multi-omics analyses was performed to compare the conditions of adding Tyr and Cystine in CHO cells. The addition of cystine resulted in decreased viability and productivity owing to endoplasmic reticulum (ER) stress and the promotion of ER-associated degradation (ERAD) and apoptosis. In contrast, addition of Tyr suppressed ER stress and apoptosis. This effect could be due to the increase in ubiquinone (Coenzyme Q10) biosynthesized from Tyr. To inhibit apoptosis caused by cystine addition, Tyr was added simultaneously with cystine, which improved growth, viability, and mAb productivity owing to the activation of GSH metabolism, suppression of ER stress and oxidative stress, reduction of ERAD, and activation of the tricarboxylic acid cycle.