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Inflammation-induced PINCH expression leads to actin depolymerization and mitochondrial mislocalization in neurons

Translational Neurodegeneration 2020年第3期9卷 393-408页

作者： Kalimuthusamy Natarajaseenivasan Santhanam Shanmughapriya Prema Velusamy Matthew Sayre Alvaro Garcia nestor mas gomez Dianne Langford Department of Neurosciences and Center for Neurovirology Lewis Katz School of Medicine at Temple UniversityPhiladelphiaPA 19140USA Department of Microbiology Bharathidasan UniversityTiruchirappalli 620024India Heart and Vascular Institute Department of MedicineDepartment of Cellular and Molecular PhysiologyPenn State College of MedicineHersheyPA 17033USA

Background:Diseases and disorders with a chronic neuroinflammatory component are often linked with changes in brain *** neurodegenerative disorders,people living with human immunodeficiency virus(HIM)and Alzheimer's disease(AD)are particularly vulnerable to metabolic disturbances,but the mechanistic connections of inflammation,neurodegeneration and bioenergetic deficits in the central nervous system(CNS)are poorly *** particularly interesting new cysteine histidine-rich-protein(PINCH)is nearly undetectable in healthy mature neurons,but is robustly expressed in tauopathy-associated neurodegenerative diseases including HIV infection and *** robust PINCH expression has been reported in neurons in the brains of patients with HIV and AD,the molecular mechanisms and cellular consequences of increased PINCH expression in CNS disease remain largely ***:We investigated the regulatory mechanisms responsible for PINCH protein-mediated changes in bioenergetics,mitochondrial subcellular localization and bioenergetic deficits in neurons exposed to physialogical levels of TNFa or the HIV protein *** in the PINCH-ILK-Parvin(PIP)complex association with cofilin and TESK1 were assessed to identify factors responsible for actin depolymerization and mitochondrial *** and pharmacological inhibition experiments were conducted to confirm PINCH specificity and to reinstate proper protein-protein complex ***:We identified MEF2A as the PINCH transcription factor in neuroinflammation and determined the biological consequences of increased PINCH in ***-mediated activation of MEF2A via increased cellular calcium induced PINCH,leading to disruption of the PIP ternary complex,cofilin activation by TESK1 inactivation,and actin *** disruption of actin led to perinuclear mislocalization of mitochondria by destabilizing the kinesin-dependent mitochondrial transport machinery,resulting i

关键词： Neuron Mitochondria Actin PINCH Neuroinflammation

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Cardiometabolic health among gastric bypass surgery patients with polycystic ovarian syndrome

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World Journal of Diabetes 2013年第3期4卷 64-69页

作者： Carley A gomez-Meade Adriana Carrillo Gabriela Lopez-Mitnik Sarah E Messiah Kristopher L Arheart nestor de la Cruz-Muoz Division of Pediatric Endocrinology Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFL 33130United States Division of Pediatric Clinical Research Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFL 33130United States Department of Epidemiology and Public Health Sciences Division of BiostatisticsUniversity of Miami Miller School of MedicineMiamiFL 33130United States Department of Surgery University of Miami Miller School of MedicineMiamiFL 33130United States

AIM:To examine the effect of gastric bypass surgery on cardiometabolic health among women with polycystic ovarian syndrome(PCOS).METHODS:Retrospective medical chart review identified women(n = 389) with PCOS who underwent Roux-en-Y gastric bypass surgery from 2001-2009 in one surgical *** repeated measures linear mixed models were fit using the MIXED procedureto assess mean change in cardiometabolic disease risk factors from before to 1-year after surgery and were evaluated by ethnicity [Hispanic,non-Hispanic black(NHB) and white(NHW)].RESULTS:The majority of the sample was Hispanic(66%,25% NHB,9% NHW).Mean body mass index significantly improved 1 year post-surgery for all ethnic groups(45.5 to 35.5 kg/m2 for Hispanics,46.8 to 37.7 kg/m2 for NHB and 45.7 to 36.7 kg/m2 for NHW,P < 0.001).Among Hispanic women mean total cholesterol(198.1 to 160.2 mg/dL),low-density lipoproteins(LDL) cholesterol(120.9 to 91.0 mg/dL),triglycerides(148.6 to 104.8 mg/dL),hemoglobin A1c(6.2% to 5.6%),alanine aminotransferase(28.1 to 23.0 U/L) and aspartate aminotransferase(23.5 to 21.6 U/L) decreased significantly(P < 0.001).Among NHB,mean total cholesterol(184.5 to 154.7 mg/dL),LDL cholesterol(111.7 to 88.9 mg/dL) and triglycerides(99.7 to 70.0 mg/dL) decreased significantly(P < 0.05).Among NHW,mean total cholesterol(200.9 to 172.8 mg/dL) and LDL cholesterol(124.2 to 96.6 mg/dL),decreased significantly(P < 0.05).Pairwise ethnic group comparisons of all cardiometabolic outcomes adjusted for age and type of surgery before and 1 year after surgery showed no statistical difference between the three groups for any ***:Cardiometabolic disease risk improvements vary by ethnicity and obesity may impact glucose tolerance and liver function changes more in Hispanic women with PCOS vs non-Hispanic women.

关键词： Bariatric surgery Polycystic ovary syndrome Cardiometabolic outcomes Weight outcomes Morbid obesity

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