Abstract 154: Stress-Induced Loss of Nuclear HMGB1 From Ischemic Muscle Is Modulated by Autophagy and Accompanies Myoblast Differentiation
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Abstract
Introduction: The nuclear protein HMGB1 can initiate innate immunity as well as sustain autophagy during times of cellular stress. We hypothesize that autophagy, a mechanism of cellular preservation, is a critical process in skeletal muscle biology during ischemia in patients with PAD. We further hypothesize that HMGB1 mobilization is associated with critical myoblast functions such as differentiation, and that this process may be modulated by autophagy.
Methods: Human C2C12 myoblasts were cultured on laminin and exposed to hypoxia (1% O2) and serum depletion. Cells were also cultured with 2% serum to induce differentiation over 72hr. C57B6 mice were injected with 3-methyladenine (3MA), an autophagy inhibitor, before femoral artery ligation (FAL) and muscles were harvested after 24hr. Cell fractions from the cultured cells and muscles were probed for HMGB1. Immunoblots were analyzed using Image J.
Results: Hypoxia and serum depletion induced complete loss of nuclear HMGB1 after 48hr. In myoblasts cultured in differentiation conditions, there was a 3 fold relative loss of nuclear HMGB1 compared with controls (p=0.014, t-test;N=3). While ischemia resulted in loss of nuclear HMGB1 in vivo, modulation of autophagic signaling with 3MA resulted in the retention of nuclear HMGB1 24 hours after FAL (Figure 1).
Conclusion: Loss of nuclear HMGB1 by stressed myoblasts during differentiation suggests that this danger signal may be important in the regulation of muscle repair after injury. Additionally, our data indicate that autophagy may play a role in controlling the mobilization of myocyte HMGB1, affecting its inflammatory and reparative functions in ischemic muscle.

Author Disclosures: J. Xu: None. X. Cui: None. G. Hong: None. E. Tzeng: None. U. Sachdev: None.
- © 2014 by American Heart Association, Inc.
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- Abstract 154: Stress-Induced Loss of Nuclear HMGB1 From Ischemic Muscle Is Modulated by Autophagy and Accompanies Myoblast DifferentiationJun Xu, Xiangdong Cui, Guiying Hong, Edith Tzeng and Ulka SachdevArteriosclerosis, Thrombosis, and Vascular Biology. 2014;34:A154, originally published September 3, 2014
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- Abstract 154: Stress-Induced Loss of Nuclear HMGB1 From Ischemic Muscle Is Modulated by Autophagy and Accompanies Myoblast DifferentiationJun Xu, Xiangdong Cui, Guiying Hong, Edith Tzeng and Ulka SachdevArteriosclerosis, Thrombosis, and Vascular Biology. 2014;34:A154, originally published September 3, 2014