title: Sucrose non-fermenting related kinase enzyme is essential for cardiac metabolism.
abstract: 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.
authors.affiliation: Department of Pediatrics, Developmental Vascular Biology Program, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Cossette
authors.affiliation: Department of Pediatrics, Developmental Vascular Biology Program, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Gastonguay
authors.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Bao
authors.affiliation: Division of Pediatric Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lerch-Gaggl
authors.affiliation: Department of Pediatrics, Developmental Vascular Biology Program, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhong
authors.affiliation: 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.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Harmann
authors.affiliation: Department of Pediatrics, Developmental Vascular Biology Program, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Koceja
authors.affiliation: Division of Pediatric Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA Division of Pediatric Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Robert Q
authors.initials: RQ
authors.lastname: Miao
authors.affiliation: Department of Pediatrics, Developmental Vascular Biology Program, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Padmanabhan
authors.initials: P
authors.lastname: Vakeel
authors.affiliation: 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.
authors.forename: Changzoon
authors.initials: C
authors.lastname: Chun
authors.affiliation: Department of Pediatrics, Developmental Vascular Biology Program, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Keguo
authors.initials: K
authors.lastname: Li
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Foeckler
authors.affiliation: Department of Pediatrics, Developmental Vascular Biology Program, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Bordas
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Weiler
authors.affiliation: 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.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Strande
authors.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Palecek
authors.affiliation: Department of Pediatrics, Developmental Vascular Biology Program, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA rramchan@mcw.edu.
authors.forename: Ramani
authors.initials: R
authors.lastname: Ramchandran
keywords: Cardiac; Fatty acid oxidation; Metabolism; SNRK; tie2