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

doi:10.1242/bio.20149811

Biology Open (Dec 2014)

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

DOI: https://doi.org/10.1242/bio.20149811
Journal volume & issue: Vol. 4, no. 1
pp. 48 – 61

Abstract

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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.

Published in Biology Open

ISSN: 2046-6390 (Online)
Publisher: The Company of Biologists
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General)
Website: https://journals.biologists.com/bio

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