RESUMO
The mitochondrial calcium uniporter (MCU) is a major protein for the uptake of mitochondrial calcium to regulate intracellular energy metabolism, including processes such as mitophagy. The present study investigated the effect of the MCU on mitophagy in pancreatic ductal epithelial cells (PDECs) in acute pancreatitis (AP) in vitro. The normal human PDECs (HPDE6-C7) were treated with caerulein (CAE) to induce AP-like changes, with or without ruthenium red to inhibit the MCU. The mitochondrial membrane potentials (MMPs) and mitochondrial Ca2+ levels were analyzed by fluorescence. The expression levels of MCU, LC3, p62, and translocase of the outer mitochondrial membrane complex subunit 20 (TOMM20), putative kinase 1 (PINK1), and Parkin were measured by western blotting and immunofluorescence. Mitophagy was observed by confocal fluorescence microscopy and transmission electron microscopy. The results showed that CAE increased the MCU protein expression, mitochondrial Ca2+ levels, MMP depolarization and the protein expression of mitophagy markers including the LC3II/I ratio, PINK1, and Parkin. CAE decreased the protein expression of p62 and TOMM20, and promoted the formation of mitophagosomes in HPDE6-C7 cells. Notably, changes in these markers were reversed by inhibiting the MCU. In conclusion, an activated MCU may promote mitophagy by regulating the PINK1/Parkin pathway in PDECs in AP.
RESUMO
BACKGROUND: Magnetic resonance (MR) imaging provides a unique, noninvasive diagnostic platform to quantify the physiological and biochemical variables of skeletal muscle at rest. This study was to investigate the difference in thigh skeletal muscles between snowboarding halfpipe athletes and healthy volunteers via multiparametric MR imaging. METHODS: A comparative study was conducted between 12 healthy volunteers and 14 snowboarding halfpipe athletes. MR scanning targeted the left leg at the level of the proximal thigh on a 3.0T MR system. The measured parameters compared between the two groups included T1, T2, T2* relaxation times, fat fraction (FF), and cross-sectional area (CSA) of the quadriceps femoris and the hamstring muscles. Statistical analysis was carried out using independent sample t-test. Interrater reliability was also assessed with intraclass correlation coefficients (ICCs). RESULTS: It was statistically equivalent between two groups in age, body mass index, thigh circumference, calf circumference, systolic blood pressure, and resting heart rate (all P > 0.05). However, the T1 and T2 values of the hamstring muscles in the athlete group were found to be significantly shorter than those in control group (T1: 1063.3 ± 24.1 ms vs. 1112.0 ± 38.2 ms in biceps femoris, 1050.4 ± 31.2 ms vs. 1095.0 ± 39.5 ms in semitendinosus, 1053.1 ± 31.7 ms vs. 1118.4 ± 40.0 ms in semimembranosus, respectively; T2: 33.4 ± 0.7 ms vs. 36.1 ± 1.9 ms in biceps femoris, 34.6 ± 2.0 ms vs. 37.0 ± 1.9 ms in semitendinosus, 36.9 ± 1.5 ms vs. 38.9 ± 2.4 ms in semimembranosus, respectively; all P < 0.05) although T2* relaxation time was detected with no significant difference. The FF of the hamstring muscles was obviously less than the control group (5.5 ± 1.9% vs. 10.7 ± 4.7%, P < 0.001). In addition, the quadriceps' CSA in the athlete group was substantially larger than the control group (8039.0 ± 1072.3 vs. 6258.2 ± 852.0 mm2, P < 0.001). Interrater reliability was excellent (ICC: 0.758-0.994). CONCLUSION: Multiple MR imaging parameters indicated significant differences between snowboarding halfpipe athletes and healthy volunteers in the thigh skeletal muscles.