Vascular endothelial cells are highly glycolytic and consume relatively low amounts of oxygen (O(2)) compared with other cells. We have confirmed that oxidative phosphorylation is not the main source of ATP generation in these cells. We also show that at a low O(2) concentration (<1%) endogenous NO plays a key role in preventing the accumulation of the alpha-subunit of hypoxia-inducible factor 1. At higher O(2) concentrations (1-3%) NO facilitates the production of mitochondrial reactive oxygen species. This production activates the AMP-activated protein kinase by a mechanism independent of nucleotide concentrations. Thus, the primary role of mitochondria in vascular endothelial cells may not be to generate ATP but, under the control of NO, to act as signaling organelles using either O(2) or O(2)-derived species as signaling molecules. Diversion of O(2) away from endothelial cell mitochondria by NO might also facilitate oxygenation of vascular smooth muscle cells.
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http://dx.doi.org/10.1073/pnas.0601026103 | DOI Listing |
Hypertension
January 2025
Department of Cardiovascular Research, Shinshu University School of Medicine, Matsumoto, Nagano, Japan. (Y. Zhao, T. Sakurai, A.K., M.T., Y.I.-S., H.K., Y.M., Y. Zhang, Q.G., P.L., K.H., M.H., J.L., T. Shindo).
Background: Adrenomedullin 2 (AM2) plays critical roles in regulating blood pressure and fluid balance. However, the specific involvement of AM2 in cardiac hypertrophy has not been comprehensively elucidated, warranting further investigation into its molecular mechanisms and therapeutic implications.
Methods: Cardiac hypertrophy was induced in adult mice lacking AM2 (AM2-/-) using transverse aortic constriction surgery.
ACS Pharmacol Transl Sci
January 2025
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Sigma 1 receptor (S1R) is a multifunctional, ligand-activated protein located in the membranes of the endoplasmic reticulum (ER). It mediates a variety of neurological disorders, including epilepsy, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease. The wide neuroprotective effects of S1R agonists are achieved by a variety of pro-survival and antiapoptotic S1R-mediated signaling functions.
View Article and Find Full Text PDFTheranostics
January 2025
Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
: Tumor associated macrophages (TAMs) are critical components in regulating the immune statuses of the tumor microenvironments. Although TAM has been intensively studied, it is unclear how mitochondrial proteins such as AGK regulate the TAMs' function. : We investigated the AGK function in TAMs using macrophage-specific deficient mice with B16 and LLC syngeneic tumor models.
View Article and Find Full Text PDFCogn Neurodyn
December 2025
Department of Mathematics, School of Technology, Pandit Deendayal Energy University, Gandhinagar, 382426 India.
A free calcium ion in the cytosol is essential for many physiological and physical functions. Also, it is known as a second messenger as the quantity of free calcium ions is an essential part of brain signaling. In this work, we have attempted to study calcium signaling in the presence of mitochondria, buffer, and endoplasmic reticulum fluxes.
View Article and Find Full Text PDFImmunometabolism (Cobham)
January 2025
Institute for Systems Biology, Seattle, WA, USA.
The nucleotide-binding domain, leucine-rich repeat, and pyrin domain containing-protein 3 (NLRP3) inflammasome is a multiprotein complex that plays a critical role in the innate immune response to both infections and sterile stressors. Dysregulated NLRP3 activation has been implicated in a variety of autoimmune and inflammatory diseases, including cryopyrin-associated periodic fever syndromes, diabetes, atherosclerosis, Alzheimer's disease, inflammatory bowel disease, and cancer. Consequently, fine-tuning NLRP3 activity holds significant therapeutic potential.
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