Biomedical subjects

Hengjun He

Publications and source records attributed to Hengjun He.

4 recordsLinked to original sources

PubMed2005

1-Pentyl-3-phenylacetylindoles, a new class of cannabimimetic indoles.

A new class of cannabimimetic indoles, with 3-phenylacetyl or substituted 3-phenylacetyl substituents, has been prepared and their affinities for the cannabinoid CB1 and CB2 receptors have been determined. In general those compounds with a 2-substituted phenylacetyl group have good affinity for both receptors. The 4-substituted analogs have little affinity for either receptor, while the 3-substituted compounds are intermediate in their affinities. Two of these compounds, 1-pentyl-3-(2-methylphenylacetyl)indole (JWH-251) and 1-pentyl-3-(3-methoxyphenylacetyl)indole (JWH-302), have 5-fold selectivity for the CB1 receptor with modest affinity for the CB2 receptor. GTPgammaS determinations indicate that both compounds are highly efficacious agonists at the CB1 receptor and partial agonists at the CB2 receptor.

Acetylation↗

PubMed2004

Arsenite induces HIF-1alpha and VEGF through PI3K, Akt and reactive oxygen species in DU145 human prostate carcinoma cells.

Arsenite is widely distributed environmental toxicant in water, food and air. It is a known human carcinogen, which is strongly associated with human cancers originated from liver, nasal cavity, lung, skin, bladder, kidney, and prostate. In this study, we investigated whether arsenite induces expression of hypoxia-inducible factor 1 (HIF-1). HIF-1 is a heterodimeric basic helix-loop-helix transcription factor, composed of HIF-1alpha and HIF-1beta/ARNT subunits; and is involved in tumor growth and angiogenesis. Here we demonstrate that arsenite induces the expression of HIF-1alpha but not HIF-1beta subunit in DU145 human prostate carcinoma cells. Arsenite also increases the expression of VEGF through the induction of HIF-1. We also found that arsenite activates PI3K and Akt that are required for arsenite-induced expression of HIF-1alpha and VEGF. The induction of HIF-1 and VEGF by arsenite can not be inhibited by MAP kinase inhibitors. Arsenite causes production of reactive oxygen species (ROS). The major species of ROS required for the induction of HIF-1 and VEGF is H2O2. These data indicate that the arsenite-induced activation of PI3K/Akt signaling and the expression of HIF-1 and VEGF through the generation of ROS could be an important mechanism in the arsenite-induced carcinogenesis.

Androstadienes↗

PubMed2004

Vanadate activated Akt and promoted S phase entry.

Protein kinase B (PKB)/Akt and its upstream signal transducer, phosphatidylinosito-3 kinase (PI3K) play an essential role in control of transcription and translation, which impact cell growth, survival, and metabolism. Transcription factor E2F is a component of the downstream proliferative machinery regulated by Akt. Hyperphosphorylation of retinoblastoma protein (pRb), a pocket protein, leads to release of E2F1, resulting in transition from G1 to S phase. The present study shows that in normal C141 cells, vanadate treatment increased the percentage of cells at S phase and elevated cyclin E and cyclin A expression. Vanadate treatment triggered phosphorylation of pRb and release of E2F1. Furthermore, vanadate increased Akt kinase activity and caused its phosphorylation at Ser473 and Thr308. Inhibition of Akt by either inhibitors or transfected cells with dominant negative kinase mutant or dominant negative phosphorylation mutant decreased the percentage of the cells at the S phase induced by vanadate, and reduced both cyclin E and E2F1 expression and phosphorylation of pRb. The present study indicates that Akt plays an essential role in vanadate-induced increase in cell number at S phase and transition from G1 to S phase through E2F-pRb pathway.

Animals↗

PubMed2004

The role of phosphatidylinositol-3 kinase in vanadate-promoted S phase entry.

Phosphatidylinositil-3 kinase (PI3K) is a heterodimer of catalytic and regulatory subunits. It is involved in various signaling pathways and key functions of the cells. The present study investigated the role of PI3K in vanadate-induced alteration in cell cycle regulation in C141 mouse epidermal cells. Vanadate caused a time- and dose-dependent increase in PI3K activity and phosphorylation of p70 S6 kinase (p70S6K) at Thr421/Ser424 and Thr389 sites. The phosphorylation at these sites was inhibited by PI3K inhibitor, LY294002, and p70S6K mutation. Vanadate promoted S phase entry and this promotion was inhibited by LY294002 and rapmycin, a p70S6K inhibitor. Vanadate-induced enhancement in S phase entry was also inhibited in transfection with dominant negative p70S6K mutant cells. The results obtained show that vanadate is able to increase PI3K activity through phosphorylation. PI3K activated p70S6K, which phosphated protein S6, and promoted S phase entry.

Animals↗