Products of oxidative and non-oxidative metabolism of L-arginine as potential regulators of Ca 2+ transport in mitochondria of uterine smooth muscle

• Published in: Biochimica et biophysica acta. General subjects 2024-06, p.130652
• Main Authors: Danylovych, Hanna V, Danylovych, Yuriy V, Pavliuk, Maksym R, Kosterin, Sergiy O
• Format: Article
• Language: English
• ISSN: 1872-8006

Mitochondria play a crucial role in maintaining Ca homeostasis in cells. Due to the critical regulatory role of the products of oxidative and non-oxidative metabolism of L-arginine, it is essential to clarify their effect on Ca transport in smooth muscle mitochondria. Experiments were performed on the uterine myocytes of rats and isolated mitochondria. The possibility of NO synthesis by mitochondria was demonstrated by confocal microscopy and spectrofluorimetry methods using the NO-sensitive fluorescent probe DAF-FM and Mitotracker Orange CM-H2TMRos. It was shown that 50 μM L-arginine stimulates the energy-dependent accumulation of Ca in mitochondria using the fluorescent probe Fluo-4 AM. A similar effect occurred when using nitric oxide donors 100 μM SNP, SNAP, and sodium nitrite (SN) directly. The stimulating effect was eliminated in the presence of the NO scavenger C-PTIO. Nitric oxide reduces the electrical potential in mitochondria without causing them to swell. The stimulatory effect of spermine on the accumulation of Ca by mitochondria is attributed to the enhancement of NO synthesis, which was demonstrated with the use of C-PTIO, NO-synthase inhibitors (100 μM NA and L-NAME), as well as by direct monitoring of NO synthesis fluorescent probe DAF-FM. A conclusion was drawn about the potential regulatory effect of the product of the oxidative metabolism of L-arginine - NO on the transport of Ca in the mitochondria of the myometrium, as well as the corresponding effect of the product of non-oxidative metabolism -spermine by increasing the synthesis of NO in these subcellular structures.