Suppression of HIV-1 Tat-induced monocyte adhesiveness by a cell-permeable superoxide dismutase in astrocytes.
HIV-1 Tat is considered to be one of key players to facilitate monocyte entry into the CNS, which is characteristic feature of AIDS-related encephalitis and dementia. This study was performed to determine the regulatory function of superoxide dismutase (SOD) on the HIV-1 Tat-induced signaling pathways leading to NF-kappaB activation, expression of adhesion molecules, and monocyte adhesion in CRT-MG human astroglioma cells by using cell-permeable SOD. When cell-permeable SOD was added to the culture medium of CRT-MG cells, it rapidly entered the cells in dose- and time-dependent manners. Treatment of astrocytes with cell-permeable SOD led to decrease in Tat-induced ROS generation as well as NF-kappaB activation. Cell-permeable SOD inhibited the activation of MAP kinases including ERK, JNK and p38 by HIV-1 Tat. Treatment of CRT-MG cells with cell-permeable SOD significantly inhibited protein and mRNA levels of ICAM-1 and VCAM-1 up-regulated by HIV-1 Tat, as measured by Western blot analysis and RT-PCR. Furthermore, enhanced adhesiveness of monocyte to astrocyte by HIV-1 Tat was significantly abrogated by pretreatment with cell-permeable SOD fusion proteins. These data indicate that SOD has a regulatory function for HIV-1 Tat-induced NF-kappaB activation in astrocytes and suggest that cell-permeable SOD can be used as a feasible therapeutic agent for regulation of ROS-related neurological diseases.
Song
Ha Yong
HY
Department of Biomedical Science, College of Natural Sciences, Hallym University, Chuncheon 200-702, Korea.
Ju
Sung Mi
SM
Lee
Ji Ae
JA
Kwon
Hyung-Joo
HJ
Eum
Won Sik
WS
Jang
Sang Ho
SH
Choi
Soo Young
SY
Park
Jinseu
J
D001253:Astrocytes / Q000201:enzymology*; D002448:Cell Adhesion / Q000502:physiology*; D002463:Cell Membrane Permeability; D015696:Gene Products, tat / Q000494:pharmacology*; D015658:HIV Infections / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*
D015696:Gene Products, tat; D013482:Superoxide Dismutase