TY - JOUR T1 - Nuclear GAPDH signaling mediates pathological cardiac hypertrophy JF - bioRxiv DO - 10.1101/844902 SP - 844902 AU - Manling Zhang AU - Taro Kariya AU - Genri Numata AU - Adrianan Ramos AU - Hideyuki Sasaki AU - Masaki Iwakiri AU - Masayuki Sasaki AU - Norimichi Koitabashi AU - Guangshuo Zhu AU - Tsuyoshi Tsujimura AU - Dong-ik Lee AU - Carlos Tristan AU - Neelam Shahani AU - Yukihiro Tsuchiya AU - Hanna Jaaro-Peled AU - Barbara Slusher AU - David A. Kass AU - Kyoji Taguchi AU - Yoshie Horiguchi AU - Toshiaki Saitoh AU - Koko Ishizuka AU - Akira Sawa AU - Eiki Takimoto Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/11/16/844902.abstract N2 - Pathological stressors disrupt cellular and organ homeostasis, causing various diseases. We discovered a novel role for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the pathological growth response of the heart, independent of its functions in glycolysis and cell death. In a cellular model for cardiac hypertrophy, endothelin-1 elicited nuclear translocation of GAPDH and activation of p300 histone acetyl-transferase (HAT), followed by activation of myocyte enhancer factor 2 (MEF2). GAPDH nuclear translocation and p300 HAT activation was also identified in rodent pathological hypertrophied hearts. The hypertrophy was markedly ameliorated by molecular and pharmacological interventions that antagonize the nuclear GAPDH pathway, including a novel antagonist selective to its nuclear function. This pathway may be the key to stress response/homeostatic control, and thus the potential therapeutic target for stress-associated diseases.One-sentence summary This study shows a novel function of GAPDH in homeostatic control of the heart, which is disturbed and results in cardiac hypertrophy with pathological stressors. ER -