Min Luo, Xiaoqun Guan, Elizabeth D. Luczak, Di Lang, William Kutschke, Zhan Gao, Jinying Yang, Patric Glynn, Samuel Sossalla, Paari D. Swaminathan, Robert M. Weiss, Baoli Yang, Adam G. Rokita, Lars S. Maier, Igor R. Efimov, Thomas J. Hund, Mark E. Anderson
Mitochondrial ROS increases ox-CaMKII and SAN cell death.
(A–C) SAN staining from WT mice treated with STZ alone and MitoTEMPO and STZ and Ncf1–/– mice treated with STZ. DAPI (blue) marks nuclei, HCN4 (green) marks SAN. Scale bars: 50 μm. (A) Representative sections show ox-CaMKII expression. Overall P = 0.006, **P < 0.01 by 1-way ANOVA (n = 3–5 per group). (B) Representative sections show TUNEL-positive cells. Overall P = 0.0006, ***P < 0.01 by 1-way ANOVA (n = 3–7 per group). (C) Fibrosis measured by Masson’s trichrome staining. Overall P = 0.016, *P < 0.05 by 1-way ANOVA (n = 3–4 per group). (D) Proposed model for CaMKII activation by STZ-induced diabetes. STZ-induced hyperglycemia and MI promote mitochondrial ROS generation, which activates ox-CaMKII to cause SND, leading to increased mortality after MI.