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Overexpression of human selenoprotein H in neuronal cells enhances mitochondrial biogenesis and function through activation of protein kinase A, protein kinase B, and cyclic adenosine monophosphate response element-binding protein pathway.
Int J Biochem Cell Biol. 2013 Mar; 45(3):604-11.IJ

Abstract

Mitochondrial biogenesis is activated by nuclear encoded transcription co-activator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which is regulated by several upstream factors including protein kinase A and Akt/protein kinase B. We have previously shown that selenoprotein H enhances the levels of nuclear regulators for mitochondrial biogenesis, increases mitochondrial mass and improves mitochondrial respiratory rate, under physiological condition. Furthermore, overexpression of selenoprotein H protects neuronal HT22 cells from ultraviolet B irradiation-induced cell damage by lowering reactive oxygen species production, and inhibiting activation of caspase-3 and -9, as well as p53. The objective of this study is to identify the cell signaling pathways by which selenoprotein H initiates mitochondrial biogenesis. We first confirmed our previous observation that selenoprotein H transfected HT22 cells increased the protein levels of nuclear-encoded mitochondrial biogenesis factors, peroxisome proliferator-activated receptor γ coactivator-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A. We then observed that total and phosphorylation of protein kinase A, Akt/protein kinase B and cyclic adenosine monophosphate response element-binding protein (CREB) were significantly increased in selenoprotein H transfected cells compared to vector transfected HT22 cells. To verify whether the observed stimulating effects on mitochondrial biogenesis pathways are caused by selenoprotein H and mediated through CREB, we knocked down selenoprotein H mRNA level using siRNA and inhibited CREB with napthol AS-E phosphate in selenoprotein H transfected cells and repeated the measurements of the aforementioned biomarkers. Our results revealed that silencing of selenoprotein H not only decreased the protein levels of PGC-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A, but also decreased the total and phosphorylation levels of protein kinase A, protein kinase B, and CREB. Similarly, CREB inhibition reduced CREB activation and PGC-1α protein levels in selenoprotein H transfected cells. Moreover, selenoprotein H transfection increased the activity of mitochondrial complexes and prevented the ultraviolet B induced fall of mitochondrial membrane potential. We conclude that the effects of selenoprotein H on mitochondrial biogenesis and mitochondrial function are probably mediated through protein kinase A-CREB-PGC-1α and Akt/protein kinase B-CREB-PGC-1α pathways.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technological Enterprise (BRITE), College of Art and Sciences, North Carolina Central University, Durham, NC 27707, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23220172

Citation

Mehta, Suresh L., et al. "Overexpression of Human Selenoprotein H in Neuronal Cells Enhances Mitochondrial Biogenesis and Function Through Activation of Protein Kinase A, Protein Kinase B, and Cyclic Adenosine Monophosphate Response Element-binding Protein Pathway." The International Journal of Biochemistry & Cell Biology, vol. 45, no. 3, 2013, pp. 604-11.
Mehta SL, Mendelev N, Kumari S, et al. Overexpression of human selenoprotein H in neuronal cells enhances mitochondrial biogenesis and function through activation of protein kinase A, protein kinase B, and cyclic adenosine monophosphate response element-binding protein pathway. Int J Biochem Cell Biol. 2013;45(3):604-11.
Mehta, S. L., Mendelev, N., Kumari, S., & Andy Li, P. (2013). Overexpression of human selenoprotein H in neuronal cells enhances mitochondrial biogenesis and function through activation of protein kinase A, protein kinase B, and cyclic adenosine monophosphate response element-binding protein pathway. The International Journal of Biochemistry & Cell Biology, 45(3), 604-11. https://doi.org/10.1016/j.biocel.2012.11.022
Mehta SL, et al. Overexpression of Human Selenoprotein H in Neuronal Cells Enhances Mitochondrial Biogenesis and Function Through Activation of Protein Kinase A, Protein Kinase B, and Cyclic Adenosine Monophosphate Response Element-binding Protein Pathway. Int J Biochem Cell Biol. 2013;45(3):604-11. PubMed PMID: 23220172.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpression of human selenoprotein H in neuronal cells enhances mitochondrial biogenesis and function through activation of protein kinase A, protein kinase B, and cyclic adenosine monophosphate response element-binding protein pathway. AU - Mehta,Suresh L, AU - Mendelev,Natalia, AU - Kumari,Santosh, AU - Andy Li,P, Y1 - 2012/12/07/ PY - 2012/09/27/received PY - 2012/11/09/revised PY - 2012/11/28/accepted PY - 2012/12/11/entrez PY - 2012/12/12/pubmed PY - 2013/9/12/medline SP - 604 EP - 11 JF - The international journal of biochemistry & cell biology JO - Int. J. Biochem. Cell Biol. VL - 45 IS - 3 N2 - Mitochondrial biogenesis is activated by nuclear encoded transcription co-activator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which is regulated by several upstream factors including protein kinase A and Akt/protein kinase B. We have previously shown that selenoprotein H enhances the levels of nuclear regulators for mitochondrial biogenesis, increases mitochondrial mass and improves mitochondrial respiratory rate, under physiological condition. Furthermore, overexpression of selenoprotein H protects neuronal HT22 cells from ultraviolet B irradiation-induced cell damage by lowering reactive oxygen species production, and inhibiting activation of caspase-3 and -9, as well as p53. The objective of this study is to identify the cell signaling pathways by which selenoprotein H initiates mitochondrial biogenesis. We first confirmed our previous observation that selenoprotein H transfected HT22 cells increased the protein levels of nuclear-encoded mitochondrial biogenesis factors, peroxisome proliferator-activated receptor γ coactivator-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A. We then observed that total and phosphorylation of protein kinase A, Akt/protein kinase B and cyclic adenosine monophosphate response element-binding protein (CREB) were significantly increased in selenoprotein H transfected cells compared to vector transfected HT22 cells. To verify whether the observed stimulating effects on mitochondrial biogenesis pathways are caused by selenoprotein H and mediated through CREB, we knocked down selenoprotein H mRNA level using siRNA and inhibited CREB with napthol AS-E phosphate in selenoprotein H transfected cells and repeated the measurements of the aforementioned biomarkers. Our results revealed that silencing of selenoprotein H not only decreased the protein levels of PGC-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A, but also decreased the total and phosphorylation levels of protein kinase A, protein kinase B, and CREB. Similarly, CREB inhibition reduced CREB activation and PGC-1α protein levels in selenoprotein H transfected cells. Moreover, selenoprotein H transfection increased the activity of mitochondrial complexes and prevented the ultraviolet B induced fall of mitochondrial membrane potential. We conclude that the effects of selenoprotein H on mitochondrial biogenesis and mitochondrial function are probably mediated through protein kinase A-CREB-PGC-1α and Akt/protein kinase B-CREB-PGC-1α pathways. SN - 1878-5875 UR - https://www.unboundmedicine.com/medline/citation/23220172/Overexpression_of_human_selenoprotein_H_in_neuronal_cells_enhances_mitochondrial_biogenesis_and_function_through_activation_of_protein_kinase_A_protein_kinase_B_and_cyclic_adenosine_monophosphate_response_element_binding_protein_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1357-2725(12)00394-9 DB - PRIME DP - Unbound Medicine ER -