Gemfibrozil is a widely used drug that elevates plasma HDL and lowers triglycerides and LDL. The mechanism of action of this pharmacological agent on HDL metabolism is not established. Since the liver is the major organ involved in HDL production and removal, we assessed the effect of gemfibrozil on the modulation of apoA-I (a major protein of HDL)-containing particles by a human hepatoblastoma cell line (Hep G2). Incubation of Hep G2 cells with gemfibrozil resulted in the following statistically significant findings: (1) increased accumulation of apoA-I in the medium without affecting uptake of radiolabeled HDL-protein or HDL-apoA-I; (2) accelerated incorporation of [3H]leucine and [35S]methionine into apoA-I; (3) equivalent increases in [3H]leucine incorporation into HDL particles without and with apoA-II (LpA-I and LpA-I+A-II, respectively); (4) equal efflux of fibroblast cholesterol by harvested LpA-I and LpA-I+A-II particles; (5) increased steady state apoA-I mRNA without affecting apoA-I transcription; and (6) increased apoA-I mRNA half-life (2.2-fold). These data indicate that gemfibrozil stabilizes apoA-I mRNA transcripts, resulting in increased translation of functional apoA-I-containing particles capable of effluxing cellular cholesterol, thus defining a major mechanism by which gemfibrozil increases HDL.

The concentration of HDL in the blood inversely correlates with the incidence of cardiovascular disease, probably related to the ability of these lipoproteins to efflux cholesterol from vascular cells. It is also possible that HDL affect the production or action of vasoactive peptides implicated in the development of vascular diseases. Therefore, we determined the effects of human HDL on the production and secretion of endothelin-1 (ET-1 ) from cultured bovine aortic endothelial cells. HDL produced a highly significant stimulation of endothelin secretion (maximum 240% of control), even at very low levels of lipoproteins (1 ,gg/ml). HDL also stimulated the translation of by twofold in the bovine aortic endothelial cells. In contrast, HDL had no significant effect on steady state mRNA levels, transcript degradation, or transcription. Stimulation of ET-1 secretion by HDL was dependent on protein kinase C activation. Purified apo A-I, the major apoprotein of HDL, increased ET-1 secretion and translation -85% as potently as HDL. Our results indicate that low concentrations of human HDL strongly stimulate the production of ET-1, a powerful vasoconstrictor and mitogen for the vascular smooth muscle cell. We propose that HDL may participate in the regulation of vasomotor tone through this potentially important effect in the vasculature. (J. Clin. Invest. 1994. 93:1056-1062

Rosiglitazone reduced SAH mortality, neurological deficits, body weight loss, GFAP loss, and cerebral vasospasm by preventing the neurotoxicity induced by glutamate and oxidative stress.

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In this study, we examined the possible apoptotic mechanism of pepsin‐digested extract of Caulerpa microphysa (CME) in myelomonocytic leukemia (WEHI‐3) cells. Flow cytometry demonstrated that CME induced cell cycle arrest in the G0/G1 phase and stimulated reactive oxygen species (ROS) production and calcium release but caused a loss of the mitochondrial membrane potential (MMP). The results indicated that the protein levels of cyclin D, cyclin E, CDK6, CDK2 and Bcl‐2 decreased and those of p21, p27, p53, Bax, Bid, GRP78, GADD153, apoptosis‐inducing factor (AIF), caspase‐3 and caspase‐9 increased in WEHI‐3 cells after CME treatment. In conclusion, CME induced G0/G1 phase arrest, decreased MMP and increased Ca2+ release and ROS production in the WEHI‐3 cells. The results suggest that CME may have potential as an anticancer agent. Practical Applications Caulerpa microphysa (CME) has multiple functions and has been applied as natural seaweed extracts in the food and pharmaceutical industries. This study revealed for the first time that CME treatments inhibited the expression of the anti‐apoptotic protein and promoted the expression of pro‐apoptotic proteins. The results suggest that CME could be functional in food and pharmaceutical industries and could be an alternative anticancer medicine in the future.

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