The Resource The effect of drugs of abuse and HIV-1 GP120 on autophagy in astrocytes, Lu Cao

The effect of drugs of abuse and HIV-1 GP120 on autophagy in astrocytes, Lu Cao

Label
The effect of drugs of abuse and HIV-1 GP120 on autophagy in astrocytes
Title
The effect of drugs of abuse and HIV-1 GP120 on autophagy in astrocytes
Statement of responsibility
Lu Cao
Creator
Contributor
Author
Degree supervisor
Subject
Genre
Language
eng
Summary
The life expectancy of individuals infected with HIV-1 has significantly improved since the introduction of highly active anti-retroviral therapy (HAART). However, this has led to an increase in the prevalence of HIV-associated neurocognitive disorders (HAND), especially the mild forms of HAND. Drugs of abuse are known to exacerbate neuropathological dysfunction in HIV-infected individuals. The neuropathological manifestation results from cell death in the CNS wherein autophagy is expected to play an important role. Autophagy is generally considered protective during deprivation or stress. However, excessive autophagy can be destructive, leading to autophagic cell death. The present study was based on the central hypothesis that drugs of abuse and HIV-1 viral proteins work synergistically in mediating autophagy in human astrocytes. The level of autophagy mediated by cocaine, methamphetamine, and HIV-1 gp120 is determined. Furthermore, we examined the cellular mechanisms responsible for cocaine and methamphetamine-mediated autophagy pathway, and the role of autophagy in drug-induced cytotoxicity. In the first chapter, we investigate the effect of cocaine on autophagy in SVGA astrocytes. We measured levels of the autophagic marker protein LC3II in SVGA astrocytes after exposure with cocaine. The results showed that cocaine caused an increase in LC3II level in a dose- and time-dependent manner. This result was also confirmed by detecting LC3II in SVGA astrocytes using confocal microscopy and transmission electron microscopy. Next, we sought to explore the mechanism by which cocaine induces the autophagic response. The involvement of sigma 1 receptor, and autophagy signaling proteins p-mTOR, Atg5, Atg7, and p-Bcl-2/Beclin-1 were determined by using selective inhibitors and siRNAs. In addition, we determined the role of autophagy in chronic cocaine exposure using MTT assay and western blot analysis. In the second chapter, the effect of methamphetamine on autophagy in SVGA astrocytes, as well as human fetal astrocytes were examined. The mechanistic pathway of methamphetamine-mediated autophagy was determined. In the third chapter, the synergistic effect of methamphetamine and HIV-1 gp120 IIIb on autophagy in SVGA astrocytic cell line and human astrocytes was determined. The signaling mechanism of methamphetamine- and gp120- mediated autophagy is investigated by utilization of specific inhibitors and siRNAs. Furthermore, the role of autophagy during methamphetamine- and gp120- induced cytotoxicity is examined by MTT assay and PI staining. In conclusion, we showed that drugs of abuse and HIV-1 viral protein gp120 were able to induce autophagy in astrocytes. The underlying mechanism provides potential therapeutic target for neuroAIDS
Cataloging source
UMK
http://library.link/vocab/creatorDate
1987-
http://library.link/vocab/creatorName
Cao, Lu
Degree
Ph.D.
Dissertation note
(School of Pharmacy).
Dissertation year
2016.
Granting institution
University of Missouri-Kansas City,
Illustrations
illustrations
Index
no index present
Literary form
non fiction
Nature of contents
  • dictionaries
  • bibliography
  • theses
http://library.link/vocab/relatedWorkOrContributorName
Anil Kumar
http://library.link/vocab/subjectName
  • Drug abuse
  • HIV infections
  • Cocaine
  • Methamphetamine
  • Autophagy
Label
The effect of drugs of abuse and HIV-1 GP120 on autophagy in astrocytes, Lu Cao
Instantiates
Publication
Copyright
Note
  • "A dissertation in Pharmacology and Pharmaceutical Sciences."
  • Advisor: Anil Kumar
  • Vita
Antecedent source
not applicable
Bibliography note
Includes bibliographical references (pages 101-125)
Carrier category
online resource
Carrier category code
  • cr
Carrier MARC source
rdacarrier
Color
black and white
Content category
text
Content type code
  • txt
Content type MARC source
rdacontent
Contents
General introduction -- General materials and methods -- The effects of cocaine on autophagy in astrocytes -- Methamphetamine potentiates HIV-1 GP120-mediated autophagy via beclin-1 and ATG5/7 as a pro-survival response in astrocytes -- Effect of antioxidants on autophagy mediated by methamphetamine and GP120 -- Summary and future directions -- Appendix
Control code
974038612
Dimensions
unknown
Extent
1 online resource (127 pages)
File format
one file format
Form of item
online
Level of compression
mixed
Media category
computer
Media MARC source
rdamedia
Media type code
  • c
Other physical details
illustrations.
Quality assurance targets
not applicable
Specific material designation
remote
System control number
(OCoLC)974038612
System details
  • The full text of the dissertation is available as an Adobe Acrobat .pdf file; Adobe Acrobat Reader required to view the file
  • Mode of access: World Wide Web
Label
The effect of drugs of abuse and HIV-1 GP120 on autophagy in astrocytes, Lu Cao
Publication
Copyright
Note
  • "A dissertation in Pharmacology and Pharmaceutical Sciences."
  • Advisor: Anil Kumar
  • Vita
Antecedent source
not applicable
Bibliography note
Includes bibliographical references (pages 101-125)
Carrier category
online resource
Carrier category code
  • cr
Carrier MARC source
rdacarrier
Color
black and white
Content category
text
Content type code
  • txt
Content type MARC source
rdacontent
Contents
General introduction -- General materials and methods -- The effects of cocaine on autophagy in astrocytes -- Methamphetamine potentiates HIV-1 GP120-mediated autophagy via beclin-1 and ATG5/7 as a pro-survival response in astrocytes -- Effect of antioxidants on autophagy mediated by methamphetamine and GP120 -- Summary and future directions -- Appendix
Control code
974038612
Dimensions
unknown
Extent
1 online resource (127 pages)
File format
one file format
Form of item
online
Level of compression
mixed
Media category
computer
Media MARC source
rdamedia
Media type code
  • c
Other physical details
illustrations.
Quality assurance targets
not applicable
Specific material designation
remote
System control number
(OCoLC)974038612
System details
  • The full text of the dissertation is available as an Adobe Acrobat .pdf file; Adobe Acrobat Reader required to view the file
  • Mode of access: World Wide Web

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