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  • Another question concerns the mechanism of

    2019-10-09

    Another question concerns the mechanism of PC reduction during the phosphate starvation response. There are at least three main mechanisms of PC depletion: suppression of PC synthesis due to substrate exhaustion, downregulation of PC synthase expression by suppression of gene transcription or intensification of mRNA degradation as well as intensive hydrolysis of PC by phospholipases. We supposed that substitution of PC by DGTS is compensatory reaction directed on phosphate release for vitally important cell processes and regulated at the level of both DGTS and PC gene transcription. Therefore we expected the decrease of mRNA abundance of PC synthesis genes. However our data provides the first evidence that the PC biosynthesis genes CPT1 and CHO2 increase their expression under phosphate-limiting conditions. These results indicate that regulation by mRNA abundance does not contribute to PC depletion during Pi-starvation in basidial fungi. What is the mechanism of elevating of mRNA abundance of PC synthesis genes – activation of synthesis or increase of stability – are the questions for future studies. The present work broadens the scope of our knowledge on the adaptive mechanism that induce DGTS synthesis in response to Pi-deficiency.
    Experimental
    Acknowledgments
    Phylogenetic analysis was carried out within the framework of the institutional research project (no. 01201255617) of the Komarov Botanical Institute of the Russian Academy of Sciences. Financial support was provided in part by the Russian Foundation for Basic Research Grants No. 14-04-01795 and 15-04-06211.
    Introduction Insulin resistance is a common feature of obesity and becoming a global public health problem leading to an increased risk for cardiovascular diseases (Riehle and Abel, 2016). Myocardial insulin resistance is characterized by the inability of cardiomyocytes to take up and use glucose as a source of Chlorogenic acid upon insulin stimulation (Riehle and Abel, 2016, Westermeier et al., 2015). Its presence alters cardiac fuel metabolism, contributing to the diabetic cardiomyopathy and other cardiac metabolic disorders (Carley and Severson, 2005, Riehle and Abel, 2016, Westermeier et al., 2015). The heart is a highly energy consuming organ. Cardiomyocytes possess high flexibility to use different substrates, especially glucose and fatty acid, for ATP production. This flexibility is adaptive to changes in fuel availability and the energy demand. Under physiological conditions, cardiomyocytes of adult heart generate 60%-70% energy from fatty acid oxidation (FAO) and about 20% from glucose oxidation in mitochondrion (Bertrand et al., 2008). While during feeding, there is a substantial shift from FAO towards increased glucose metabolism. The increased FAO can inhibit glucose oxidation, a regulation referred as glucose-fatty acid cycle or Randle cycle (Randle et al., 1963). Although the heart can functionally tolerate various pathophysiological changes, adaptive responses might eventually fail upon sustained insults such as overnutrition and obesity, leading to mitochondrial stress and metabolic remodeling, which is considered an early event in the progression of cardiac metabolic diseases (Harvey and Leinwand, 2011). Several studies have demonstrated that lipid overload induces increased FAO, resulting in myocardial insulin resistance and subsequent damage to heart (Abel et al., 2012, Griffin et al., 2016, Zhang et al., 2010, Nobuhara et al., 2013). In this context, metabolic intervention at the early stage is beneficial. Ginsenosides are the major effective components of ginseng and notoginseng, two well-known medicinal herbs widely used in China for treatment of cardiovascular diseases and type 2 diabetes. However, compared to the main ginsenosides such as Rb1 and Rg1, rare ginsenosides receive less attention and their bioactivities remain to be dissected. Our previous work has showed that a rare ginsenoside-standardized extract (RGSE), derived from steamed notoginseng, and Rg5, a main rare ginsenoside in RGSE, can reduce acute cardiac ischemic injury (Wang et al., 2015, Yang et al., 2017). Rg5 also impacts lipolysis and ameliorates insulin signaling in skeletal muscle (Xiao et al., 2017). These studies prompt us to explore specific effects of rare ginsenosides on cardiac metabolic abnormalities.