Chemical alterations and regulations of biomolecules in lifestyle-related diseases

Abstract

We know experientially that not only nutrient factors but also non-nutritive functional food factors are playing important roles in maintenance of homeostasis, health promotion, and disease prevention. Although some of these effective behaviors are supported by accumulating scientific evidences, it is in general difficult to determine properly in human. Therefore, the discovering of novel biomarker and developments of the analytical method are one of the prudent strategies to understand disease etiology and evaluate efficacies of functional food factors via monitoring the pathophysiological alteration in live body, tissue, and cells. This review describes recent our findings on (1) formation mechanism, bioactivities, quantitative determination of cholesterol ozonolysis product, secosterol as possible biomarker for lifestyle-related disease, and (2) chemical biology approach for the investigating molecular mechanisms of most promising cancer chemopreventive food factors, isothiocyanate-inducing bioactivities.

Nanodelivery of natural isothiocyanates as a cancer therapeutic

“…In general, ITCs can react readily with sulfur-, nitrogen-and oxygen-based biological nucleophiles, e.g. the thiol and amino groups of proteins [11]. Thus, the biological activities of ITCs may be due to the direct reaction with these functional groups in various proteins.…”

Biochemical properties of cholesterol aldehyde secosterol and its derivatives

“…High levels of secosterol-A and secosterol-B have been detected in human atherosclerotic plaques ( 13 ) and tissues samples of brains affected by neurodegeneration, such as Alzheimer’s disease and Lewy body dementia, ( 25 , 26 ) suggesting that increased formation of these compounds may be associated with inflammation-related diseases. ( 27 , 28 ) For the analysis of secosterol-A and secosterol-B in clinical samples, HPLC separation with UV, fluorescence, or MS(/MS) detection have been widely employed. In general, lipid extracts of blood or tissues containing secosterol-A and secosterol-B are derivatized with hydrazine derivatives, such as dinitrophenylhydrazine (DNPH), then injected to HPLC or LC-MS. ( 13 , 29 ) For the higher sensitive detection, derivatization with dansyl (DNSL) hydrazine (LOD = 1 fmol), ( 21 , 23 , 26 ) 1-pyrenebutyric hydrazine (PBH; LOD = 10 fmol), ( 30 ) Girard P (GP) hydrazine (LOD = 2.7 fmol), ( 31 ) or 2-hydrazino-1-methylpyridine (HMP; LOD = 10–50 amol) ( 32 ) are applicable.…”

The Contribution of Singlet Oxygen to Insulin Resistance

“…Singlet oxygen but not free radical oxidation readily converts cholesterol to cholesterol-5-hydroperoxide (29), which, under acidic conditions, undergoes Hock cleavage to form cholesterol secosterol aldehyde A (30), followed by rapid acid-catalyzed aldolization of the latter to form secosterol B (31) ( Figure 5 ), so that secosterol A is only detected as a minor product under such conditions [ 115 , 118 ]. On the other hand, ozonolysis of cholesterol affords secosterol A as the main product [ 115 , 118 , 119 ]. Both secosterol aldehydes A and B have been isolated in significant quantities from various human tissues and LDL, confirming the importance of singlet oxygen, ozone, and/or an ozone-like oxidant in in vivo lipid oxidation [ 115 , 118 , 119 ].…”

“…On the other hand, ozonolysis of cholesterol affords secosterol A as the main product [ 115 , 118 , 119 ]. Both secosterol aldehydes A and B have been isolated in significant quantities from various human tissues and LDL, confirming the importance of singlet oxygen, ozone, and/or an ozone-like oxidant in in vivo lipid oxidation [ 115 , 118 , 119 ]. These aldehydes were also detected in the plasma and other tissues of normal mice, further supporting the formation of singlet oxygen in endothelial cells and other cell types independently of leukocyte activation and inflammation [ 120 ].…”

“…These aldehydes were also detected in the plasma and other tissues of normal mice, further supporting the formation of singlet oxygen in endothelial cells and other cell types independently of leukocyte activation and inflammation [ 120 ]. The fact that secosterol A is a major product in vivo was interpreted as evidence for endogenous ozone formation [ 115 , 118 , 119 ]. Potential mechanisms for the antibody- or amino acid-catalyzed endogenous ozone formation in the presence of singlet oxygen have been proposed [ 119 , 121 ].…”