<p>Endozepine is an alternative name for the testis-specific isoform of the acyl-CoA binding protein (t-ACBP). Acyl-CoA binding proteins form a highly conserved family of proteins, which bind long chain fatty acid esters with nanomolar affinity. They are also known to be endogenous ligands to the --amino butyric acid (GABA) receptor in the central nervous system and to play a role in a wide variety of cellular functions such as vesicular trafficking, fatty acid biosynthesis and gene regulation. A role for endozepine in apoptosis was suggested through promoter gene trapping studies using CHO22 cells in which 90 % reduction in the expression of endozepine correlated with delayed mitochondrial permeabilization, a reduced activation of caspase-3 (an activator of apoptosis) and a consequent resistance to C2-ceramide induced apoptosis.</p> <p>Transduction studies using Tat-GFP-ELP fusion protein showed that endozepine restored the sensitivity of mutant CHO22 cells to C2-ceramide induced apoptosis. In this thesis, we have investigated two hypotheses for the involvement of endozepine in ceramide-induced apoptosis. The first hypothesis is that endozepine contributes to apoptosis through the transport of palmitoyl-CoA, a substrate required for the de novo synthesis of ceramide. The second hypothesis is that endozepine interacts directly with ceramide leading to interaction with peripheral benzodiazepine receptor and a subsequent opening of the mitochondria permeability transition pore, leading to apoptosis.</p>

<p>Endozepine is an alternative name for the testis-specific isoform of the acyl-CoA binding protein (t-ACBP). Acyl-CoA binding proteins form a highly conserved family of proteins, which bind long chain fatty acid esters with nanomolar affinity. They are also known to be endogenous ligands to the --amino butyric acid (GABA) receptor in the central nervous system and to play a role in a wide variety of cellular functions such as vesicular trafficking, fatty acid biosynthesis and gene regulation. A role for endozepine in apoptosis was suggested through promoter gene trapping studies using CHO22 cells in which 90 % reduction in the expression of endozepine correlated with delayed mitochondrial permeabilization, a reduced activation of caspase-3 (an activator of apoptosis) and a consequent resistance to C2-ceramide induced apoptosis.</p> <p>Transduction studies using Tat-GFP-ELP fusion protein showed that endozepine restored the sensitivity of mutant CHO22 cells to C2-ceramide induced apoptosis. In this thesis, we have investigated two hypotheses for the involvement of endozepine in ceramide-induced apoptosis. The first hypothesis is that endozepine contributes to apoptosis through the transport of palmitoyl-CoA, a substrate required for the de novo synthesis of ceramide. The second hypothesis is that endozepine interacts directly with ceramide leading to interaction with peripheral benzodiazepine receptor and a subsequent opening of the mitochondria permeability transition pore, leading to apoptosis.</p>

Epidemiological studies have shown that cholesterol is a major risk factor for the development of atherosclerosis. Since the atherosclerotic plaque develops over a long period interventions early in life may be of some benefit. In addition, it has been shown that the enzymes involved in cholesterol metabolism can be manipulated in early life. Therefore, studies of the developmental patterns of the key enzymes in cholesterol metabolism are of great importance. Acyl coenzyme A: cholesterol acyltransferase (ACAT) is the primary enzyme which catalyzes the conversion of free cholesterol to cholesterol esters in cells. A better understanding of the role and control of ACAT during development is needed in order to trace the possible causes in early life that lead to atherosclerosis in the adult. This research focused on the developmental pattern of ACAT in the rat liver, intestine, brown and white adipose tissue (BAT and WAT, respectively) and aorta. Age specific changes were observed in the rat liver, intestine and BAT. The rat liver and intestine possess significant amounts of ACAT activity throughout development and there appears to be marked variations in activity during this time. The rat BAT and WAT appear to be devoid of ACAT activity throughout development with the exception of adult BAT. Due to the small amount of the aortic tissue samples and/or the insensitivity of the assay, no definite conclusions could be made from this aortic study. In searching for factors that might control the ACAT enzyme the immediate effects of short-term manipulation of diet on the activity of ACAT were studied. The rats were all weaned early on day 18 to one of the following diets: Purina Rat Chow, high carbohydrate (HG) , high fat (HF) , or 2% cholesterol. The HF was the only diet that consistently increased hepatic ACAT activity in all the age groups. The cholesterol diets significantly increased the activity of ACAT in the 22 and 25 day old rats. The HG diet increased the activity of ACAT in the 22, 25, and 30 day old rats. No significant differences were observed between the adult control and HG diet groups. Feeding rats a HF or HG diet precipitated a dramatic drop in intestinal ACAT activity in the 22 day old animals. These effects were not observed in the older animals. The high cholesterol diet had no significant effect on the intestinal enzyme's activity in 22 day old rats. There was no significant change in the BAT and WAT ACAT activity with the experimental diets with the exception that all the experimental diets decreased ACAT activity in the adult BAT. / Medicine, Faculty of / Medicine, Department of / Experimental Medicine, Division of / Graduate

Magister Scientiae - MSc / Endozepine is an alternative name for the testis-specific isoform of the acyl-CoA binding protein (t-ACBP). Acyl-CoA binding proteins form a highly conserved family of proteins, which bind long chain fatty acid esters with nanomolar affinity. They are also known to be endogenous ligands to the --amino butyric acid (GABA) receptor in the central nervous system and to play a role in a wide variety of cellular functions such as vesicular trafficking, fatty acid biosynthesis and gene regulation. A role for endozepine in apoptosis was suggested through promoter gene trapping studies using CHO22 cells in which 90 % reduction in the expression of endozepine correlated with delayed mitochondrial permeabilization, a reduced activation of caspase-3 (an activator of apoptosis) and a consequent resistance to C2-ceramide induced apoptosis. Transduction studies using Tat-GFP-ELP fusion protein showed that endozepine restored the sensitivity of mutant CHO22 cells to C2-ceramide induced apoptosis. In this thesis, we have investigated two hypotheses for the involvement of endozepine in ceramide-induced apoptosis. The first hypothesis is that endozepine contributes to apoptosis through the transport of palmitoyl-CoA, a substrate required for the de novo synthesis of ceramide. The second hypothesis is that endozepine interacts directly with ceramide leading to interaction with peripheral benzodiazepine receptor and a subsequent opening of the mitochondria permeability transition pore, leading to apoptosis. / South Africa

Thesis (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2006. / Embargoed. Vita. Bibliography: 217-242.

Forty-five Angus steers (358 kg BW) were utilized in a completely randomized block design with a 3 x 3 factorial arrangement of treatments to evaluate the hypothesis that differing dietary linolenic acid (from corn, flaxseed plus corn, or milo) and whole cottonseed (WCS) inclusion (0, 5, or 15% DM) would interact to alter fatty acid metabolism and deposition of conjugated linoleic acid (CLA) in subcutaneous (s.c.) and interfasicular (i.f.) adipose tissues, and thereby decrease carcass quality score. During the feeding period (135 d), steers receiving flaxseed or corn diets had a greater gain:feed ratio (0.119 and 0.108, respectively) than steers receiving the milo diet (0.093). Following transportation to a local abattoir and overnight starvation, there was less decrease in weight in flaxseed-fed steers (1.51%) than in steers fed the corn (2.89%) or milo diets (3.11%). Ribeye area of steers fed milo was less than that of steers fed the corn or flaxseed diets. Lipogenesis from acetate in s.c. adipose tissue was greater in steers fed flaxseed (5.42 nmol h-1 105 cells-1) than in the corn (3.10 nmol h-1 105 cells-1) or milo (1.92 nmol h-1 105 cells-1) groups. Stearoyl-CoA desaturase (SCD) activity in s.c. adipose tissue was unchanged between the 0% WCS group (88.1 nmol mg protein-1 7 min-1) and the 15% WCS group (20 nmol mg protein-1 7 min-1). The i.f. saturated fatty acid percentages increased with increasing levels of WCS. The i.f. cis-9, trans-11 CLA percentage increased with increasing WCS in the steers fed the corn diet, whereas it remained unchanged or even decreased slightly in the steers fed the flaxseed or milo-based diets. Steers fed flaxseed had a greater s.c. adipose concentration of vaccenic acid (18:1trans-11) than the steers fed milo. Steers fed flaxseed also had greater s.c. and i.f. percentages of linolenic acid (18:3, n-3) than steers fed either of the other grain sources. Increased dietary linolenic acid from flaxseed may have increased s.c. adipocyte volume by stimulating lipogenesis. These data indicate that rations formulated to provide increased levels of linolenic acid (i.e., flaxseed) will increase feed efficiency and lipogenesis from acetate without altering either the quality or composition of the beef carcasses.

Forty-five Angus steers (358 kg BW) were utilized in a completely randomized block design with a 3 x 3 factorial arrangement of treatments to evaluate the hypothesis that differing dietary linolenic acid (from corn, flaxseed plus corn, or milo) and whole cottonseed (WCS) inclusion (0, 5, or 15% DM) would interact to alter fatty acid metabolism and deposition of conjugated linoleic acid (CLA) in subcutaneous (s.c.) and interfasicular (i.f.) adipose tissues, and thereby decrease carcass quality score. During the feeding period (135 d), steers receiving flaxseed or corn diets had a greater gain:feed ratio (0.119 and 0.108, respectively) than steers receiving the milo diet (0.093). Following transportation to a local abattoir and overnight starvation, there was less decrease in weight in flaxseed-fed steers (1.51%) than in steers fed the corn (2.89%) or milo diets (3.11%). Ribeye area of steers fed milo was less than that of steers fed the corn or flaxseed diets. Lipogenesis from acetate in s.c. adipose tissue was greater in steers fed flaxseed (5.42 nmol h-1 105 cells-1) than in the corn (3.10 nmol h-1 105 cells-1) or milo (1.92 nmol h-1 105 cells-1) groups. Stearoyl-CoA desaturase (SCD) activity in s.c. adipose tissue was unchanged between the 0% WCS group (88.1 nmol mg protein-1 7 min-1) and the 15% WCS group (20 nmol mg protein-1 7 min-1). The i.f. saturated fatty acid percentages increased with increasing levels of WCS. The i.f. cis-9, trans-11 CLA percentage increased with increasing WCS in the steers fed the corn diet, whereas it remained unchanged or even decreased slightly in the steers fed the flaxseed or milo-based diets. Steers fed flaxseed had a greater s.c. adipose concentration of vaccenic acid (18:1trans-11) than the steers fed milo. Steers fed flaxseed also had greater s.c. and i.f. percentages of linolenic acid (18:3, n-3) than steers fed either of the other grain sources. Increased dietary linolenic acid from flaxseed may have increased s.c. adipocyte volume by stimulating lipogenesis. These data indicate that rations formulated to provide increased levels of linolenic acid (i.e., flaxseed) will increase feed efficiency and lipogenesis from acetate without altering either the quality or composition of the beef carcasses.