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Increased vulnerability of ApoE4 neurons to HIV proteins and opiates: protection by diosgenin and L-deprenyl.
Neurobiol Dis. 2006 Jul; 23(1):109-19.ND

Abstract

Human immunodeficiency virus (HIV) infection continues to rise in drug-abusing populations and causes a dementing illness in a subset of individuals. Factors contributing to the development of dementia in this population remain unknown. We found that HIV-infected individuals with the E4 allele of Apolipoprotein E (ApoE) or history of intravenous drug abuse had increased oxidative stress in the CNS. In vitro studies showed that HIV proteins, gp120 and Tat, Tat + morphine but not tumor necrosis factor-alpha (TNF-alpha), caused increased neurotoxicity in human neuronal cultures with ApoE4 allele. Microarray analysis showed a differential alteration of transcripts involved in energy metabolism in cultures of ApoE3 and 4 neurons upon treatment with Tat + morphine. This was confirmed using assays of mitochondrial function and exposure of the neurons to Tat + morphine. Using this in vitro model, we screened a number of novel antioxidants and found that only L-deprenyl and diosgenin protected against the neurotoxicity of Tat + morphine. Furthermore, Tat-induced oxidative stress impaired morphine metabolism which could also be prevented by diosgenin. In conclusion, opiate abusers with HIV infection and the ApoE4 allele may be at increased risk of developing dementia. L-deprenyl and a plant estrogen, diosgenin, may have therapeutic potential in this population.

Authors+Show Affiliations

Departments of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40546, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16697650

Citation

Turchan-Cholewo, Jadwiga, et al. "Increased Vulnerability of ApoE4 Neurons to HIV Proteins and Opiates: Protection By Diosgenin and L-deprenyl." Neurobiology of Disease, vol. 23, no. 1, 2006, pp. 109-19.
Turchan-Cholewo J, Liu Y, Gartner S, et al. Increased vulnerability of ApoE4 neurons to HIV proteins and opiates: protection by diosgenin and L-deprenyl. Neurobiol Dis. 2006;23(1):109-19.
Turchan-Cholewo, J., Liu, Y., Gartner, S., Reid, R., Jie, C., Peng, X., Chen, K. C., Chauhan, A., Haughey, N., Cutler, R., Mattson, M. P., Pardo, C., Conant, K., Sacktor, N., McArthur, J. C., Hauser, K. F., Gairola, C., & Nath, A. (2006). Increased vulnerability of ApoE4 neurons to HIV proteins and opiates: protection by diosgenin and L-deprenyl. Neurobiology of Disease, 23(1), 109-19.
Turchan-Cholewo J, et al. Increased Vulnerability of ApoE4 Neurons to HIV Proteins and Opiates: Protection By Diosgenin and L-deprenyl. Neurobiol Dis. 2006;23(1):109-19. PubMed PMID: 16697650.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased vulnerability of ApoE4 neurons to HIV proteins and opiates: protection by diosgenin and L-deprenyl. AU - Turchan-Cholewo,Jadwiga, AU - Liu,Yiling, AU - Gartner,Suzanne, AU - Reid,Rollie, AU - Jie,Chunfa, AU - Peng,Xuejun, AU - Chen,Kuey Chu C, AU - Chauhan,Ashok, AU - Haughey,Norman, AU - Cutler,Roy, AU - Mattson,Mark P, AU - Pardo,Carlos, AU - Conant,Katherine, AU - Sacktor,Ned, AU - McArthur,Justin C, AU - Hauser,Kurt F, AU - Gairola,Chandra, AU - Nath,Avindra, Y1 - 2006/05/11/ PY - 2005/11/21/received PY - 2006/01/25/revised PY - 2006/02/11/accepted PY - 2006/5/16/pubmed PY - 2006/9/7/medline PY - 2006/5/16/entrez SP - 109 EP - 19 JF - Neurobiology of disease JO - Neurobiol Dis VL - 23 IS - 1 N2 - Human immunodeficiency virus (HIV) infection continues to rise in drug-abusing populations and causes a dementing illness in a subset of individuals. Factors contributing to the development of dementia in this population remain unknown. We found that HIV-infected individuals with the E4 allele of Apolipoprotein E (ApoE) or history of intravenous drug abuse had increased oxidative stress in the CNS. In vitro studies showed that HIV proteins, gp120 and Tat, Tat + morphine but not tumor necrosis factor-alpha (TNF-alpha), caused increased neurotoxicity in human neuronal cultures with ApoE4 allele. Microarray analysis showed a differential alteration of transcripts involved in energy metabolism in cultures of ApoE3 and 4 neurons upon treatment with Tat + morphine. This was confirmed using assays of mitochondrial function and exposure of the neurons to Tat + morphine. Using this in vitro model, we screened a number of novel antioxidants and found that only L-deprenyl and diosgenin protected against the neurotoxicity of Tat + morphine. Furthermore, Tat-induced oxidative stress impaired morphine metabolism which could also be prevented by diosgenin. In conclusion, opiate abusers with HIV infection and the ApoE4 allele may be at increased risk of developing dementia. L-deprenyl and a plant estrogen, diosgenin, may have therapeutic potential in this population. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/16697650/Increased_vulnerability_of_ApoE4_neurons_to_HIV_proteins_and_opiates:_protection_by_diosgenin_and_L_deprenyl_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(06)00037-4 DB - PRIME DP - Unbound Medicine ER -