Neuronal PINCH is regulated by TNF-α and is required for neurite extension.
During HIV infection of the CNS, neurons are damaged by viral proteins, such as Tat and gp120, or by inflammatory factors, such as TNF-α, that are released from infected and/or activated glial cells. Host responses to this damage may include the induction of survival or repair mechanisms. In this context, previous studies report robust expression of a protein called particularly interesting new cysteine histidine-rich protein (PINCH), in the neurons of HIV patients' brains, compared with nearly undetectable levels in HIV-negative individuals (Rearden et al., J Neurosci Res 86:2535-2542, 2008), suggesting PINCH's involvement in neuronal signaling during HIV infection of the brain. To address potential triggers for PINCH induction in HIV patients' brains, an in vitro system mimicking some aspects of HIV infection of the CNS was utilized. We investigated neuronal PINCH expression, subcellular distribution, and biological consequences of PINCH sequestration upon challenge with Tat, gp120, and TNF-α. Our results indicate that in neurons, TNF-α stimulation increases PINCH expression and changes its subcellular localization. Furthermore, PINCH mobility is required to maintain neurite extension upon challenge with TNF-α. PINCH may function as a neuron-specific host-mediated response to challenge by HIV-related factors in the CNS.
Jatiani
Asavari
A
Department of Neuroscience, Temple University School of Medicine, 3500 N. Broad St., MERB 750, Philadelphia, PA, USA.
Pannizzo
Paola
P
Gualco
Elisa
E
Del-Valle
Luis
L
Langford
Dianne
D
D015526:AIDS Dementia Complex / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000821:virology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D047468:Immunoprecipitation; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C088088:LIMS1 protein, human; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus