HIV-1 gp120 induces autophagy in cardiomyocytes via the NMDA receptor.
BACKGROUND
HIV-1 envelope glycoprotein gp120 (gp120) is considered as one of the major virulent proteins responsible for the involvement of the cardiovascular system. Autophagy as a form of self maintenance plays important roles in cell survival and death. HIV-1 gp120 is reported to induce autophagy in a variety of cells. However, the effect of gp120 on autophagy in cardiomyocytes has not been reported. This study aimed to test our hypothesis that gp120 could induce autophagy in cardiomyocytes.


METHODS
Rat cardiomyocyte H9c2 cells were treated with gp120 (100 ng/ml) in vitro for 4h, 1 day and 7 days. The autophagy related proteins were analyzed by Western blot and the autophagosomes were analyzed by confocal microscopy.


RESULTS
The autophagic proteins and autophagosomes were markedly increased in the H9c2 cells after 4h of gp120 treatment. Furthermore, gp120 induced autophagic proteins and autophagosomes were significantly inhibited by the N-methyl-d-aspartic acid (NMDA) receptor inhibitor MK801, c-Jun N-terminal kinase (JNK) inhibitor SP600125, and the class III phosphoinositide 3-kinase (PI3K) inhibitor 3-methyladenine (3-MA), while there was no change in the cells pretreated with the CXCR4 antagonist AMD3100. In addition, no apparent cell death was observed in the cardiomyocytes treated with gp120 for up to 7 days.


CONCLUSIONS
In summary, our research demonstrated for the first time that HIV-1 gp120 could induce autophagy of cardiomyocytes and the NMDA receptor, JNK and class III PI3K were involved in this process. This observation provides a new insight into the mechanisms of in the cardiovascular involvement during HIV-1 infection.
Department of Cardiology, Laboratory for Vascular and Oncology Research, The First Affiliated Hospital, China Medical University, 92 North 2nd Road, Heping District, Shenyang, Liaoning Province, Post Code 110001, China.
Liang
L
Meng
Zixin
Z
Zhang
Ke
K
Xu
Guoxian
G
Qi
D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology*; D002460:Cell Line; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000633:toxicity*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D015699:HIV Envelope Protein gp120; D016194:Receptors, N-Methyl-D-Aspartate; C514793:gp120 protein, Human immunodeficiency virus 1