Sucrose non-fermenting related kinase enzyme is essential for cardiac metabolism
Stephanie M. Cossette,
Adam J. Gastonguay,
Xiaoping Bao,
Alexandra Lerch-Gaggl,
Ling Zhong,
Leanne M. Harmann,
Christopher Koceja,
Robert Q. Miao,
Padmanabhan Vakeel,
Changzoon Chun,
Keguo Li,
Jamie Foeckler,
Michelle Bordas,
Hartmut Weiler,
Jennifer Strande,
Sean P. Palecek,
Ramani Ramchandran
Affiliations
Stephanie M. Cossette
Department of Pediatrics, Developmental Vascular Biology Program, Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Adam J. Gastonguay
Department of Pediatrics, Developmental Vascular Biology Program, Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Xiaoping Bao
Department of Chemical and Biological Engineering, University of Wisconsin, Madison, WI 53706, USA
Alexandra Lerch-Gaggl
Division of Pediatric Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Ling Zhong
Department of Pediatrics, Developmental Vascular Biology Program, Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Leanne M. Harmann
Division of Cardiovascular Medicine, Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Clinical and Translational Science Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Christopher Koceja
Department of Pediatrics, Developmental Vascular Biology Program, Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Robert Q. Miao
Division of Pediatric Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Padmanabhan Vakeel
Department of Pediatrics, Developmental Vascular Biology Program, Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Changzoon Chun
Division of Nephrology, Hypertension and Renal Transplantation, College of Medicine, University of Florida, Gainesville, FL 32610, USA. Department of Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA
Keguo Li
Department of Pediatrics, Developmental Vascular Biology Program, Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Jamie Foeckler
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226, USA
Michelle Bordas
Department of Pediatrics, Developmental Vascular Biology Program, Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Hartmut Weiler
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226, USA
Jennifer Strande
Division of Cardiovascular Medicine, Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Sean P. Palecek
Department of Chemical and Biological Engineering, University of Wisconsin, Madison, WI 53706, USA
Ramani Ramchandran
Department of Pediatrics, Developmental Vascular Biology Program, Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA
In this study, we have identified a novel member of the AMPK family, namely Sucrose non-fermenting related kinase (Snrk), that is responsible for maintaining cardiac metabolism in mammals. SNRK is expressed in the heart, and brain, and in cell types such as endothelial cells, smooth muscle cells and cardiomyocytes (CMs). Snrk knockout (KO) mice display enlarged hearts, and die at postnatal day 0. Microarray analysis of embryonic day 17.5 Snrk hearts, and blood profile of neonates display defect in lipid metabolic pathways. SNRK knockdown CMs showed altered phospho-acetyl-coA carboxylase and phospho-AMPK levels similar to global and endothelial conditional KO mouse. Finally, adult cardiac conditional KO mouse displays severe cardiac functional defects and lethality. Our results suggest that Snrk is essential for maintaining cardiac metabolic homeostasis, and shows an autonomous role for SNRK during mammalian development.
