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Na/K-ATPase ALPHα1 Regulates Adipogenesis via Its Conserved Caveolin Binding Motif
Get PDFThe Na/K-ATPase (NKA) was identified in 1957 by Dr. Jens C. Skou. It belongs to the P-type ATPase family, which can actively transport ions across cell membranes by using the energy from adenosine triphosphate (ATP) hydrolysis. During the second half of the 20th century, the molecular mechanism of the NKA catalytic cycle was clarified, and the isoform diversity of NKA in different species and organs was identified. The active ion transport through NKA generates cell membrane ion gradients and the electric potential. Hence, the enzymatic function of NKA is critical for cell viability as well as multiple physiological processes including muscle contraction, renal sodium reabsorption, and nerve impulse transmission. Inhibition of NKA-mediated ion transport by cardiotonic steroids (CTS), which have long been used in the clinical treatment of heart failure, improves cardiac inotropy. Moreover, CTS at low concentrations were found to induce signal transduction through NKA, revealing its receptor signaling function. In addition to its role as an ion pump, the NKA α1 isoform forms a signal receptor complex with the non-receptor tyrosine kinase Src and the scaffolding protein caveolin1 (Cav1). The gain of the caveolin binding motif (CBM) in the α1 NKA is required for the nonion pumping function of NKA and the early stages of organogenesis in mice and C. elegans.
Considering the reported importance of NKA non-ion-pumping function in metabolic disorders, we further tested whether the loss of this CBM altered adiposity in mice and impaired adipogenesis in a human induced pluripotent stem cell (iPSC) model. At the age of 6-months, NKA CBM mutant (mCBM) heterozygous mice exhibit altered adiposity and reduced white adipose tissue (WAT) mass. The histology of mCBM WAT indicated tissue fibrosis and chronic inflammation, which may contribute to adipose tissue metabolic dysfunction. To further understand the molecular mechanism, we used an mCBM human iPSC model and a differentiation protocol to mimic the adipogenesis process in vitro. These studies indicated that the loss of CBM function in NKA α1 in human iPSC induces extracellular matrix (ECM) fibrotic remodeling. The ECM remodeling does not block the commitment of stem cells into adipocytes. However, it results in increased oxidative stress, insulin resistance, chronic inflammation, and eventually metabolic dysfunction during adipogenesis.
Thus, we characterized a novel role of the non-ion pumping NKA and its interaction with Cav1 in the regulation of stem cell differentiation and adipogenesis. This provides novel insight into the complex dynamic of regulation of caveolar structure and function in the adipocyte and could be of therapeutic relevance in the management of fat-related disorders ranging from genetic lipodystrophies to metabolic syndromes
Girl Scouts working on a badge
No full textGirl Scouts working on a badge during Girl Scout Badge College, Saturday, November 13, 2021, on the Marshall University, Huntington campus.https://mds.marshall.edu/bd_girl_scout_badge_college_2021/1011/thumbnail.jp
Kavanaugh User Guide
No full textThe User Guide for the Library of Appalachian Preaching is a Google Sheet that can be searched, sorted, and downloaded for offline use.
At the moment, Kavanaugh has only one sermon in the Library; it has a Guide of its own so the records will be complete. It includes the title, sermon text, date and place the sermon was preached, and so on. This information is available in the master list of sermons as well.https://mds.marshall.edu/kavanaugh_hubbardhinde/1001/thumbnail.jp
Simpson User Guide
No full textThe User Guide for the Library of Appalachian Preaching is a Google Sheet that can be searched, sorted, and downloaded for offline use.
This part of the Guide provides information about Simpson\u27s sermons and addresses. It includes the title, scripture text, date and place the discourse was delivered (if known), and so on. This information is available in the master list of sermons as well.https://mds.marshall.edu/simpson_matthew/1002/thumbnail.jp