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.

Sucrose Non-Fermenting Related Kinase Expression in Ovarian Cancer and Correlation with Clinical Features

“…Sections were blocked for non-specific binding in 1.5% normal goat serum and incubated with the primary SNRK antibody (1:100; Abcam, ab96762) overnight at 4°C. The specificity of this antibody for SNRK has been previously validated by our lab(8). For negative controls, a section from each sample was incubated in PBS without primary antibody.…”

“…Studies show it is involved in neuronal apoptosis(6), blood vessel development(7), and cardiac development, metabolism and function in mammals(8). SNRK is also reported to directly phosphorylate the mTOR binding partner raptor which results in inhibition of mTOR complex 1 (mTORC1) and causes cell cycle arrest(9).…”

Sucrose Nonfermenting-Related Kinase Enzyme–Mediated Rho-Associated Kinase Signaling is Responsible for Cardiac Function

“…Methodologies related to protein estimation, quantitation were described previously 7 . The following antibodies were used: anti- myosin-binding subunit (MBS; BioLegend), anti-phospho MBS (pMBS; Cell Signaling Technology/MBL International); anti-ROCK1 (BD Bioscience); anti-ROCK2 (BD Bioscience); anti-extracellular signal-regulated kinase (ERK; Cell Signaling Technology); anti-phospho ERK (pERK; Cell Signaling Technology); anti-protein kinase B (AKT; Cell Signaling Technology); anti-phospho AKT (pAKT; Cell Signaling Technology); anti-inhibitor of kappa B kinase (IKK; Cell Signaling Technology); anti-phospho IKK(pIKK; Cell Signaling Technology); anti-Tubulin (Sigma), anti-rabbit horseradish peroxidase (HRP; Cell Signaling Technology) and anti-mouse HRP (Cell Signaling Technology).…”

“…In our previous work 7 , we reported that the global Snrk KO mice die within 24 hours after birth, displayed enlarged hearts, and lethality is associated with metabolic defects in cardiac tissues. SNRK maintains metabolic homeostasis via regulation of the phosphorylated acetyl-coA carboxylase (pACC)-phosphorylated AMPK (pAMPK) pathway during this transitional period in development 7 . Furthermore, cardiac specific conditional Snrk KO ( Snrk cmcKO) adult mice display severe cardiac functional deficits and lethality within 8–10 months.…”

“…To date signaling molecules regulating ROCK activity have primarily been restricted to the RhoA pathway. Our lab has identified a novel member of the AMP-activated kinase (AMPK) family namely sucrose non-fermenting related kinase (SNRK) that is essential for angiogenesis 6 , and responsible for cardiac metabolism in mammals 7 . Here, we implicate SNRK as a putative regulator of ROCK activity in cardiomyocytes (CMs).…”