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Abstract
Hypothermic conditions enhance the incidence of cardiovascular diseases due to increased blood pressure. Cold-induced adaptive thermogenesis increased mitochondrial biogenesis and function in skeletal muscles and adipocytes. Here, we studied the effect of intermittent cold exposure on the regulators of cardiac mitochondrial biogenesis, function, and its regulation by SIRT-3. Intermittent cold exposed mice hearts showed normal histopathology with increased mitochondrial antioxidant and metabolic function, as evidenced by an increase in the activity and expression of MnSOD and SDH. A substantial increase in mitochondrial DNA copy number and increase in the expression of PGC-1α and its downstream targets NRF-1 and Tfam indicated the possibility of enhanced cardiac mitochondrial biogenesis and function on intermittent cold exposure. Increased mitochondrial SIRT-3 level and decreased total protein lysine acetylation indicate increased sirtuin activity in cold exposed mice hearts. Ex vivo cold mimic using norepinephrine showed a significant increase in PGC-1α, NRF-1, and Tfam levels. AGK-7, a SIRT-3 inhibitor, reversed the norepinephrine-induced upregulation of PGC-1α and NRF-1, indicating the role of SIRT-3 on the production of PGC-1α and NRF-1. Inhibition of PKA with KT5720 in norepinephrine treated cardiac tissue slices indicates the role of PKA in regulating the production of PGC-1α and NRF-1. In conclusion, intermittent cold exposure upregulated the regulators of mitochondrial biogenesis and function through PKA and SIRT-3 mediated pathway. Our results emphasize the role of intermittent cold-induced adaptive thermogenesis in overcoming chronic cold-induced cardiac damage.
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Editor-in-Chief
László ROSIVALL (Semmelweis University, Budapest, Hungary)
Managing Editor
Anna BERHIDI (Semmelweis University, Budapest, Hungary)
Co-Editors
- Gábor SZÉNÁSI (Semmelweis University, Budapest, Hungary)
- Ákos KOLLER (Semmelweis University, Budapest, Hungary)
- Zsolt RADÁK (University of Physical Education, Budapest, Hungary)
- László LÉNÁRD (University of Pécs, Hungary)
- Zoltán UNGVÁRI (Semmelweis University, Budapest, Hungary)
Assistant Editors
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- Zsuzsanna MIKLÓS (Semmelweis University, Budapest, Hungary)
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Hungarian Editorial Board
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- Zoltán BENYÓ (Semmelweis University, Budapest, Hungary)
- Mihály BOROS (University of Szeged, Hungary)
- László CSERNOCH (University of Debrecen, Hungary)
- Magdolna DANK (Semmelweis University, Budapest, Hungary)
- László DÉTÁRI (Eötvös Loránd University, Budapest, Hungary)
- Zoltán GIRICZ (Semmelweis University, Budapest, Hungary and Pharmahungary Group, Szeged, Hungary)
- Zoltán HANTOS (Semmelweis University, Budapest and University of Szeged, Hungary)
- Zoltán HEROLD (Semmelweis University, Budapest, Hungary)
- László HUNYADI (Semmelweis University, Budapest, Hungary)
- Gábor JANCSÓ (University of Pécs, Hungary)
- Zoltán KARÁDI (University of Pecs, Hungary)
- Miklós PALKOVITS (Semmelweis University, Budapest, Hungary)
- Gyula PAPP (University of Szeged, Hungary)
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- András SPÄT (Semmelweis University, Budapest, Hungary)
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- József TOLDI (MTA-SZTE Neuroscience Research Group and University of Szeged, Hungary)
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