Role of omega-3 and omega-6 endocannabinoids in cardiopulmonary pharmacology.

Endocannabinoids are derived from dietary omega-3 and omega-6 fatty acids and play an important role in regulation of inflammation, development, neurodegenerative diseases, cancer, and cardiovascular diseases. They elicit this effect via interactions with cannabinoid receptors 1 and 2 which are also targeted by plant derived cannabinoid from cannabis. The evidence of the involvement of the endocannabinoid system in cardiopulmonary function comes from studies that show that cannabis consumption leads to cardiovascular effect such as arrythmia and is beneficial in lung cancer patients. Moreover, omega-3 and omega-6 endocannabinoids play several important roles in cardiopulmonary system such as causing airway relaxation, suppressing atherosclerosis and hypertension. These effects are mediated via the cannabinoids receptors that are abundant in the cardiopulmonary system. Overall, this chapter reviews the known role of phytocannabinoids and endocannabinoids in the cardiopulmonary context.

Cholesterol twists the transmembrane Di-Gly region of amyloid-precursor protein.

Nearly 95% of Alzheimer's disease (AD) occurs sporadically without genetic linkage. Aging, hypertension, high cholesterol content, and diabetes are known nongenomic risk factors of AD. Aggregation of Aß peptides is an initial event of AD pathogenesis. Aß peptides are catabolic products of a type I membrane protein called amyloid precursor protein (APP). Aß40 is the major product, whereas the 2-residue-longer version, Aß42, induces amyloid plaque formation in the AD brain. Since cholesterol content is one risk factor for sporadic AD, we aimed to explore whether cholesterol in the membrane affects the structure of the APP transmembrane region, thereby modulating the γ-secretase cutting behavior. Here, we synthesized several peptides containing the APP transmembrane region (sequence 693-726, corresponding to the Aß22-55 sequence) with one or two Cys mutations for spin labeling. We performed three electron spin resonance experiments to examine the structural changes of the peptides in liposomes composed of dioleoyl phosphatidylcholine and different cholesterol content. Our results show that cholesterol increases membrane thickness by 10% and peptide length accordingly. We identified that the di-glycine region of Aß36-40 (sequence VGGVV) exhibits the most profound change in response to cholesterol compared with other segments, explaining how the presence of cholesterol affects the γ-secretase cutting site. This study provides spectroscopic evidence showing how cholesterol modulates the structure of the APP transmembrane region in a lipid bilayer.