Dystrophin deficiency affects human astrocyte properties andresponse to damage

Objective. To investigate the effect of isoflurane (ISO) on the proliferation, apoptosis, and inflammatory response of lipopolysaccharide- (LPS-) induced normal human astrocytes (NHAs) by regulating the miR-206/BDNF axis. Methods. NHA proliferation activity was measured by MTT; NHA apoptotic rates were measured by Annexin V-FITC/PI; western blotting was used to measure the BDNF expression; ELISA was used to measure the IL-6, IL-1β, and TNF-α expression in NHAs; qPCR was used to measure the expressions of miRNAs that are related to NHAs proliferation and apoptosis; dual-luciferase reporter was constructed to validate the targeting relationship between miR-206 and BDNF. Results. LPS increased the proliferation activity and decreased the apoptosis rate of NHAs which were effectively reversed by the ISO (p<0.05); LPS significantly inhibited the expression of miRNAs related to proliferation and apoptosis in NHAs (p<0.05, p<0.01), whereas ISO significantly increased the expression of miR-206 (p<0.01) by downregulating the expression of BDNF, thus inhibiting NHA proliferation and inflammatory response and enhancing apoptosis. Conclusion. ISO can inhibit the expression of BDNF by upregulating the expression of miR-206, thereby inhibiting the proliferation and inflammatory response of NHAs and promoting its apoptosis.

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Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models

JRSM Cardiovascular Disease ◽

10.1177/2048004019879581 ◽

2019 ◽

Vol 8 ◽

pp. 204800401987958

Author(s):

HR Spaulding ◽

C Ballmann ◽

JC Quindry ◽

MB Hudson ◽

JT Selsby

Keyword(s):

Skeletal Muscle ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Disease Progression ◽

Gene Mutations ◽

Dystrophin Gene ◽

Mdx Mice ◽

Dystrophin Deficiency ◽

Muscle Wasting Disease ◽

Dystrophin Protein

Background Duchenne muscular dystrophy is a muscle wasting disease caused by dystrophin gene mutations resulting in dysfunctional dystrophin protein. Autophagy, a proteolytic process, is impaired in dystrophic skeletal muscle though little is known about the effect of dystrophin deficiency on autophagy in cardiac muscle. We hypothesized that with disease progression autophagy would become increasingly dysfunctional based upon indirect autophagic markers. Methods Markers of autophagy were measured by western blot in 7-week-old and 17-month-old control (C57) and dystrophic (mdx) hearts. Results Counter to our hypothesis, markers of autophagy were similar between groups. Given these surprising results, two independent experiments were conducted using 14-month-old mdx mice or 10-month-old mdx/Utrn± mice, a more severe model of Duchenne muscular dystrophy. Data from these animals suggest increased autophagosome degradation. Conclusion Together these data suggest that autophagy is not impaired in the dystrophic myocardium as it is in dystrophic skeletal muscle and that disease progression and related injury is independent of autophagic dysfunction.

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Cytokine regulation of CD40 expression in fetal human astrocyte cultures

Journal of Neuroimmunology ◽

10.1016/s0165-5728(99)00124-1 ◽

1999 ◽

Vol 101 (1) ◽

pp. 7-14 ◽

Cited By ~ 25

Author(s):

Nahed Abdel-Haq ◽

Hsiao-Nan Hao ◽

William D. Lyman

Keyword(s):

Cytokine Regulation ◽

Human Astrocyte ◽

Cd40 Expression

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Dystrophin deficiency, altered cell signalling and fibre hypertrophy

Neuromuscular Disorders ◽

10.1016/0960-8966(94)90066-3 ◽

1994 ◽

Vol 4 (4) ◽

pp. 305-315 ◽

Cited By ~ 17

Author(s):

O. Hardiman

Keyword(s):

Cell Signalling ◽

Dystrophin Deficiency ◽

Altered Cell

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Dystrophin-deficiency increases the susceptibility to doxorubicin-induced cardiotoxicity

European Journal of Heart Failure ◽

10.1016/j.ejheart.2007.07.016 ◽

2007 ◽

Vol 9 (10) ◽

pp. 986-994 ◽

Cited By ~ 14

Author(s):

Shiwei Deng ◽

Bettina Kulle ◽

Mehdi Hosseini ◽

Gregor Schlüter ◽

Gerd Hasenfuss ◽

...

Keyword(s):

Dystrophin Deficiency

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gp120-induced alterations of human astrocyte function: Na+/H+exchange, K+conductance, and glutamate flux

AJP Cell Physiology ◽

10.1152/ajpcell.2000.279.3.c700 ◽

2000 ◽

Vol 279 (3) ◽

pp. C700-C708 ◽

Cited By ~ 42

Author(s):

Holly K. Patton ◽

Zhen-Hong Zhou ◽

James K. Bubien ◽

Etty N. Benveniste ◽

Dale J. Benos

Keyword(s):

Glutamate Uptake ◽

Cell Types ◽

Neurological Complications ◽

Ph Sensitive ◽

Human Astrocyte ◽

Physiological Processes ◽

Human Astrocytes ◽

Rat Astrocytes ◽

Immunodeficiency Syndrome ◽

Intracellular Alkalinization

Many human immunodeficiency virus (HIV)-infected patients suffer from impaired neurological function and dementia. This facet of the disease has been termed acquired immunodeficiency syndrome (AIDS)-associated dementia complex (ADC). Several cell types, including astrocytes and neurons, are not productively infected by virus but are involved in ADC pathophysiology. Previous studies of rat astrocytes showed that an HIV coat protein (gp120) accelerated astrocyte Na+/H+exchange and that the resultant intracellular alkalinization activated a pH-sensitive K+conductance. The present experiments were conducted to determine whether gp120 affected human astrocytes in the same fashion. It was found that primary human astrocytes express a pH-sensitive K+conductance that was activated on intracellular alkalinization. Also, gp120 treatment of whole cell clamped human astrocytes activated this conductance specifically. Furthermore, gp120 inhibited glutamate uptake by primary human astrocytes. These altered physiological processes could contribute to pathophysiological changes in HIV-infected brains. Because the gp120-induced cell physiological changes were partially inhibited by dimethylamiloride (an inhibitor of Na+/H+exchange), our findings suggest that modification of human astrocyte Na+/H+exchange activity may provide a means of addressing some of the neurological complications of HIV infection.

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