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Photobiomodulation (PBM) therapy, a therapeutic approach utilizing low-level light, has garnered significant attention for its potential to modulate various biological processes. This study aimed at optimizing and investigating the effects of PBM on angiogenesis and mitochondrial metabolic activity. In vitro experiments using human umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (VSMCs) were performed to assess PBM's impacts on cell migration, proliferation, endogenous protoporphyrin IX production, mitochondrial membrane potential, Rhodamine 123 fluorescence lifetime, mitochondrial morphology, and oxygen consumption. Our findings demonstrated that the PBM approach significantly stimulates HUVECs and VSMCs, highlighting the importance of precise light dosimetry for optimal outcomes. Interestingly, our results indicate that in our conditions, the optimal radiometric and spectral parameters are similar for HUVECs and VSMCs for the different endpoints mentioned above. In conclusion, our study strongly suggests that PBM holds promise as a therapeutic intervention for conditions characterized by impaired angiogenesis, such as wound healing, ischemia, and cardiovascular disease. Further research is necessary to fully elucidate the underlying mechanisms and optimize the radiometric and spectral parameters for clinical applications. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (APOE) has been strongly implicated in the development of diet induced obesity. In the present study, we investigated the contribution of brain and peripherally expressed human apolipoprotein E3 (APOE3), the most common human isoform, to diet induced obesity. In our studies APOE3 knock-in ( Apoe3 knock - in ), Apoe-deficient ( apoe −/− ) and brain-specific expressing APOE3 ( Apoe3 brain ) mice were fed western-type diet for 12 week and biochemical analyses were performed. Moreover, AAV-mediated gene transfer of APOE3 to apoe −/− mice was employed, as a means to achieve APOE3 expression selectively in periphery, since peripherally expressed APOE does not cross blood brain barrier (BBB) or blood-cerebrospinal fluid barrier (BCSFB). Our data suggest a bimodal role of APOE3 in visceral white adipose tissue (WAT) mitochondrial metabolic activation that is highly dependent on its site of expression and independent of postprandial dietary lipid deposition. Our findings indicate that brain APOE3 expression is associated with a potent inhibition of visceral WAT mitochondrial oxidative phosphorylation, leading to significantly reduced substrate oxidation, increased fat accumulation and obesity. In contrast, peripherally expressed APOE3 is associated with a notable shift of substrate oxidation towards non-shivering thermogenesis in visceral WAT mitochondria, leading to resistance to obesity. [ABSTRACT FROM AUTHOR]

p32 [also known as HABP1 (hyaluronan-binding protein 1), gC1qR (receptor for globular head domains complement 1q) or C1qbp (complement 1q-binding protein)] has been shown previously to have both mitochondrial and non-mitochondrial localization and functions. In the present study, we show for the first time that endogenous p32 protein is a mitochondrial protein in HeLa cells under control and stress conditions. In defining the impact of altering p32 levels in these cells, we demonstrate that the overexpression of p32 increased mitochondrial fibrils. Conversely, siRNA-mediated p32 knockdown enhanced mitochondrial fragmentation accompanied by a loss of detectable levels of the mitochondrial fusion mediator proteinsMfn (mitofusin) 1 and Mfn2. More detailed ultrastructure analysis by transmission electron microscopy revealed aberrant mitochondrial structures with less and/or fragmented cristae and reduced mitochondrial matrix density as well as more punctate ER (endoplasmic reticulum)with noticeable dissociation of their ribosomes. The analysis of mitochondrial bioenergetics showed significantly reduced capacities in basal respiration and oxidative ATP turnover following p32 depletion. Furthermore, siRNA-mediated p32 knockdown resulted in differential stress-dependent effects on cell death, with enhanced cell death observed in the presence of hyperosmotic stress or cisplatin treatment, but decreased cell death in the presence of arsenite. Taken together, our studies highlight the critical contributions of the p32 protein to the morphology of mitochondria and ER under normal cellular conditions, as well as important roles of the p32 protein in cellular metabolism and various stress responses. [ABSTRACT FROM AUTHOR]

Adipose organ is made of white (WAT) and brown (BAT) adipose tissue which are primarily responsible for lipid storage and energy production (heat and ATP) respectively. Metabolic activation of WAT may ascribe to this tissue characteristics of BAT, namely non-shivering thermogenesis and ATP production. Recent data indicate that apolipoproteins E (APOE) and A1 (APOA1) regulate WAT mitochondrial metabolic activation. Here, we investigated the functional cross-talk between natural human APOE2 and APOE4 isoforms with APOA1 in this process, using Apoe2 knock-in and Apoe4 knock-in mice. At baseline when Apoe2 knock-in and Apoe4 knock-in mice express both APOE and Apoa1, the Apoe2 knock-in strain appears to have higher mitochondrial oxidative phosphorylation levels and non-shivering thermogenesis in WAT compared to Apoe4 knock-in mice. When mice were switched to a high-fat diet for 18 weeks, circulating levels of endogenous Apoa1 in Apoe2 knock-in mice became barely detectable though significant levels of APOE2 were still present. This change was accompanied by a significant reduction in WAT mitochondrial Ucp1 expression while BAT Ucp1 was unaffected. Ectopic APOA1 expression in Apoe2 knock-in animals potently stimulated WAT but not BAT mitochondrial Ucp1 expression providing further evidence that APOA1 potently stimulates WAT non-shivering thermogenesis in the presence of APOE2. Ectopic expression of APOA1 in Apoe4 knock-in mice stimulated BAT but no WAT mitochondrial Ucp1 levels, suggesting that in the presence of APOE4, APOA1 is a trigger of BAT non-shivering thermogenesis. Overall, our data identified a tissue-specific role of the natural human APOE2 and APOE4 isoforms in WAT- and BAT-metabolic activation respectively, that appears dependent on circulating APOA1 levels. • Distinct effects of APOE2 and APOE4 on BAT and WAT mitochondrial metabolism • The metabolic effects of APOE2 and APOE4 on BAT and WAT depend on APOA1. • Ectopic APOA1 in Apoe2 knock-in mice raises WAT but no BAT mitochondrial Ucp1 levels. • Ectopic APOA1 in Apoe4 knock-in mice raises BAT but no WAT mitochondrial Ucp1 levels. [ABSTRACT FROM AUTHOR]