ABSTRACT
BACKGROUND: PTEN-induced kinase 1 (PINK1) is a serine/threonine-protein kinase in mitochondria that is critical for mitochondrial quality control. PINK1 triggers mitophagy, a selective autophagy of mitochondria, and is involved in mitochondrial regeneration. Although increments of mitochondrial biogenesis and activity are known to be crucial during differentiation, data regarding the specific role of PINK1 in osteogenic maturation and bone remodeling are limited. METHODS: We adopted an ovariectomy model in female wildtype and Pink1-/- mice. Ovariectomized mice were analyzed using micro-CT, H&E staining, Masson's trichrome staining. RT-PCR, western blot, immunofluorescence, alkaline phosphatase, and alizarin red staining were performed to assess the expression of PINK1 and osteogenic markers in silencing of PINK1 MC3T3-E1 cells. Clinical relevance of PINK1 expression levels was determined via qRT-PCR analysis in normal and osteoporosis patients. RESULTS: A significant decrease in bone mass and collagen deposition was observed in the femurs of Pink1-/- mice after ovariectomy. Ex vivo, differentiation of osteoblasts was inhibited upon Pink1 downregulation, accompanied by impaired mitochondrial homeostasis, increased mitochondrial reactive oxygen species production, and defects in mitochondrial calcium handling. Furthermore, PINK1 expression was reduced in bones from patients with osteoporosis, which supports the practical role of PINK1 in human bone disease. CONCLUSIONS: In this study, we demonstrated that activation of PINK1 is a requisite in osteoblasts during differentiation, which is related to mitochondrial quality control and low reactive oxygen species production. Enhancing PINK1 activity might be a possible treatment target in bone diseases as it can promote a healthy pool of functional mitochondria in osteoblasts.
Subject(s)
Mitochondria , Mitophagy , Protein Kinases/metabolism , Animals , Cell Differentiation , Female , Homeostasis , Humans , Mice , Mitochondria/genetics , Mitochondria/metabolism , Mitophagy/genetics , Osteoblasts/metabolism , Protein Serine-Threonine KinasesABSTRACT
[This corrects the article on p. 1084 in vol. 31, PMID: 27756119.].
ABSTRACT
BACKGROUND/AIMS: This study appraised the long term clinical outcomes of patients treated with percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) disease. There are limited data regarding long-term clinical outcomes after PCI for ULMCA disease. METHODS: From 2001 to 2011, a total of 448 patients who underwent PCI for ULMCA disease and had 2-year clinical follow-up, were analyzed. The study patients were divided into two groups: group I (stable angina pectoris [SAP], n = 60, 48 men, 62 ± 10 years) and group II (acute coronary syndrome [ACS], n = 388, 291 men, 64 ± 10 years). We evaluated clinical and angiographic characteristics and major adverse cardiac events (MACE) during 2-year clinical follow-up. RESULTS: Mean age of studied patients was 64 ± 10 years with 339 male patients. Average stent diameter was 3.6 ± 0.4 mm and stent length was 19.7 ± 6.3 mm. Stent implantation techniques and use of intravascular ultrasound guidance were not different between two groups. In-hospital mortality was 0% in group I and 7% in group II (p = 0.035). One-month mortality was 0% in group I and 7.7% in group II (p = 0.968). Two-year survival rate was 93% in the group I and 88.4% in the group II (p = 0.921). Predictive factors for 2-year MACE were hypertension, Killip class ≥ 3, and use of intra-aortic balloon pump by multivariate analysis. CONCLUSIONS: Although in-hospital mortality rate was higher in ACS than in SAP, clinical outcomes during 2-year clinical follow-up were similar between SAP and ACS after PCI of ULMCA.
Subject(s)
Acute Coronary Syndrome/therapy , Angina, Stable/therapy , Coronary Artery Disease/therapy , Percutaneous Coronary Intervention , Acute Coronary Syndrome/diagnostic imaging , Acute Coronary Syndrome/mortality , Aged , Angina, Stable/diagnostic imaging , Angina, Stable/mortality , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Disease Progression , Disease-Free Survival , Drug-Eluting Stents , Female , Hospital Mortality , Humans , Intra-Aortic Balloon Pumping/adverse effects , Male , Middle Aged , Multivariate Analysis , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Percutaneous Coronary Intervention/mortality , Proportional Hazards Models , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
Both nucleophilicities and accessibilities of three alkanolamines [monoethanolamine (MEA), (2-(methylamino)ethanol (MAE), and 2-amino-2-methyl-1-propanol (AMP)] were calculated to predict their reactivities with CO(2). After DFT geometry-optimization calculations, the global, group, and atomic nucleophilicities of each amine were obtained using MP2 quantum mechanical calculations. Only global nucleophilicity matched an experimental pK(a) order (MAE > AMP > MEA). However, it failed to predict the slow rate of the sterically hindered AMP and the order of rate constants, MAE > MEA > AMP. The accessibilities of amines to CO(2) have been calculated by MD simulations by monitoring collisions at the reaction centers: N atoms in amines and C in CO(2). The accessibility results indicate that global nucleophilicity needs quantitative correction for steric effects to predict better reactivities of amines with CO(2).
Subject(s)
Alcohols/chemistry , Amines/chemistry , Carbon Dioxide/chemistry , Absorption , Molecular Dynamics Simulation , Molecular Structure , Quantum Theory , Surface PropertiesABSTRACT
A crystal structure of a carbamate of 2-amino-2-methyl-1-propanol (AMP-carbamate) has been elucidated and its structural and electronic properties investigated by density functional theory calculations and natural bond orbital analyses.
