Triggering of inflammatory response by myeloperoxidase-oxidized LDL.

The oxidation theory proposes that LDL oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis in triggering inflammation. In contrast to the copper-modified LDL, there are few studies using myeloperoxidase-modified LDL (Mox-LDL) as an inflammation inducer. Our aim is to test whether Mox-LDL could constitute a specific inducer of the inflammatory response.

Ghrelin degradation by serum and tissue homogenates: identification of the cleavage sites.

The endogenous ligand for the GH secretagogue receptor is ghrelin, a peptide recently purified from the stomach. Ghrelin is n-octanoylated on the Ser(3) residue, and this modification is essential for its interaction with the receptor. The degradation of ghrelin by rat and human serum, purified commercial enzymes, and tissues homogenates was analyzed by combining HPLC and mass spectrometry.

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) modulate several biochemical pathways in human leukemic myeloid cells.

The neuropeptides Vasoactive-intestinal peptide (VIP) and Pituitary adenylate-cyclase activating protein (PACAP) increased cAMP levels in three out of five human myeloid leukemic cell lines tested while an increased in calcium intracytoplasmic levels was seen only in one cell line (HEL). This increase was phospholipase C, Pertussis toxin dependent and associated with an increase in c-fos and c-jun protein expression together with the formation of functional AP-1 transcriptional factor complex. Cell exposure to VIP or PACAP resulted in a decrease in HEL cell proliferation associated with a down-regulation of the erythroid marker, Glycophorin A.

Impairment of beta-adrenergic signaling in healthy peripheral blood mononuclear cells exposed to serum from patients with septic shock: involvement of the inhibitory pathway of adenylyl cyclase stimulation.

The objective of this study was to determine whether the serum of patients with sepsis could alter the capability of healthy human peripheral blood mononuclear cells (PBMC) to synthesize cAMP in response to beta-adrenergic stimulation and to evaluate the involvement of the inhibitory pathway (Gi) of adenylyl cyclase in the sepsis-induced alteration of beta-adrenergic signaling. First, PBMC from a healthy donor were incubated for 24 h in serum-containing medium according to three culture conditions: serum alone, serum with pertussis toxin, and serum with propranolol. Second, PBMC were stimulated with 10(-5) M isoproterenol or 10(-6) M forskolin, and measurement of cyclic adenosine monophosphate (cAMP) intracellular accumulation was performed.