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It has been reported previously that the offspring of rat dams consuming low dietary copper (Cu) during pregnancy and lactation experience a deficiency in cardiac cytochrome c oxidase (CCO) characterized by reduced catalytic activity and mitochondrial and nuclear subunit content after postnatal d 10. The present study was undertaken to determine whether the cardiac CCO deficiency was caused directly by low postnatal Cu intake or whether it was a prenatal effect of low Cu intake by the dams that became manifest postnatally. Dams were fed either a Cu-adequate diet (6 mg Cu/kg) or Cu- deficient diet (1 mg Cu/kg) beginning 3 wk before conception and throughout gestation and lactation. One day following parturition, several litters from Cu-adequate dams were cross fostered to Cu-deficient dams and several litters from Cu-deficient dams were cross fostered to Cu-adequate dams. Litters that remained with their birth dams served as controls. CCO activity, the content of the mitochondrial-encoded CCO subunit 1 (COX1), and the content of the nuclear- encoded subunit COX4 in cardiac mitochondria were reduced in the 21-d-old offspring of Cu-deficient dams. COX1 content was normal in the 21-d-old cross-fostered offspring of Cu-deficient dams, but CCO activity and COX4 were reduced. Cross fostering the offspring of Cu-adequate dams to Cu-deficient dams did not significantly affect CCO activity, COX1 content, or COX4 content in cardiac mitochondria of 21-d-old offspring. These data indicate that low prenatal Cu intake by dams was the determinant of CCO activity in cardiac mitochondria of the 21-d-old offspring and may have led to the assembly of a less-than-fully active holoenzyme.

It has been documented that dietary copper (Cu) deficiency impairs mitochondrial respiratory function, which is catalyzed by 5 membrane-bound multiple protein complexes. However, there are few reports on the simultaneous analysis of Cu effect on the subunit protein expression on all 5 protein complexes. The present study was undertaken to determine the effect of Cu deficiency on each mitochondrial respiratory complex's protein expression in rat heart tissue with western-blot analysis. Male Sprague-Dawley rats were fed diets that were either Cu adequate (6.0 [micro]g Cu/g diet, n = 5) or Cu deficient (0.3 [micro]g Cu/g diet, n = 5) for 5 wk. The monoclonal antibody-based western-blot analysis suggested that the protein levels of 39-kDa and 30-kDa subunits in complex I; 70-kDa and 30-kDa subunits in complex II; core I and core II subunits in complex III; and [alpha] and [beta] subunits of F1 complex in complex V in both high-salt buffer (HSB) and low-salt buffer (LSB) protein fractions from heart tissue of Cu-deficient rats did not differ from those of Cu-adequate rats. However, the protein level of cytochrome c oxidase (CCO) subunit (COX) I, COX Vb, and COX Vlb subunits in complex IV (CCO) in both HSB and LSB protein fractions from heart tissue of Cu-deficient rats was lower than those of Cu-adequate rats. Collectively, these data demonstrate that Cu deficiency decreases each tested subunit protein expression of complex IV but not those of complex I, II, 111, and V in mitochondrial respiratory complexes.

The trace element copper (Cu) is a required nutrient in the diets of humans. It has been found in animal studies to be essential for efficient iron absorption and oxygen utilization and for aiding free-radical degradation. Dry beans (Phaseolis vulgaris) are potentially good sources of Cu; thus, the objective of this study was to determine the bioavailability of Cu from dry beans using the pinto bean as the source. Dry beans were obtained from a local market, cooked according to package directions, and dried. Weanling male Sprague-Dawley rats (8 groups of 8 rats each) were fed a Cu-deficient diet (AIN-93G) for 4 wk followed by 2 wk of Cu repletion with diets containing 0-6.5 mg Cu/kg diet added as CuS[O.sub.4] or with 0.6 and 1.5 mg Cu/kg incorporated into rat diets as pinto beans at 10 and 20%. Standard response curves were developed based on repletion-induced recovery of 10 indices of Cu status, including organ Cu concentrations and Cu-dependent enzyme activities, in response to increasing dietary Cu as CuS[O.sub.4]. Recovery of these variables in rats fed the pinto bean diets was compared with the standard response curve at similar levels of dietary Cu. Based on the recovery of all 10 variables, the relative bioavailability of Cu from dry beans was at least 100% of that with the highly available CuS[O.sub.4]. For 3 of the variables, liver and heart Cu concentrations and serum superoxide dismutase 3 activity, estimated bioavailability values of Cu from beans were 138, 140, and 134%, respectively, of those from CuS[O.sub.4]. We conclude that the dry pinto bean is a good source of dietary Cu with respect to both concentration and bioavailability.

The mechanism for reduced Fe absorption in Cu deficiency is unknown, but may involve the intestinal Cu-dependent ferroxidase, Hephaestin (Hp). A 2 x 2 factorial experiment was designed to include Cu-deficient (CUD) and Cu-adequate (CuA) male and female rats. Weanling rats of both sexes were randomly divided into 2 groups each and fed an AIN-93G diet with tow (< 0.3 mg/kg; CuD) or adequate Cu (5.0 mg/kg; CuA). After 19 d, rats were fed 1.0 g each of their respective diets labeled with [sup.59]Fe. Retained [sup.59]Fe was monitored by whole-body counting for 12 d. Then, rats were killed for [sup.59]Fe and Fe measurements in blood and various organs. Duodenal enterocytes were isolated for Western blot analysis of Hp. Signs of Cu and Fe deficiency were evident in both sexes. CuD male rats absorbed 60% as much Fe as CuA male rats (P < 0.001), whereas CuD female rats absorbed 70% (P < 0.001) as much as CuA females, with no difference between the sexes. Hp protein in enterocytes of CuD rats of both sexes was only 35% of that in CuA rats. The biological half-life of [sup.59]Fe in CuD rats was only 50% (P < 0.001) of that in CuA rats, suggesting that Fe turnover was faster in CuD rats than CuA rats. Serum, spleen, and kidney Fe were lower (P < 0.001) in CuD rats than in CuA rats. Duodenal mucosa and liver Fe were higher (P < 0.01) in CuD male rats than CuA rats. Duodenal Fe but not liver Fe was higher in CuD female rats than CuA rats. Liver Fe was much higher ( KEY WORDS: * copper deficiency * iron * absorption * biological half-life * rats

The activity of hepatic heme oxygenase (HO) in rats is elevated in response to copper deficiency. However, the mechanism responsible for the increase in HO activity is poorly understood. Oxidative stress is a common denominator for many of the signals that induce HO-1, the inducible isoform of HO. The present study evaluated the role of [H.sub.2][O.sub.2] and the mitochondrial electron transport chain as a potential mechanism for the induction of HO-1 during copper deficiency. Mitochondria isolated from the livers of young male rats fed a copper-deficient diet for 5 wk had significantly (P < 0.05) reduced levels of NADH:cytochrome c reductase (31% reduction), succinate:cytrochrome c reductase (42% reduction), and cytochrome c oxidase (70% reduction) activities and significantly increased production of [H.sub.2][O.sub.2] (48% increase) when glutamate was used as a substrate. Hepatic levels of HO-1 protein and mRNA were also significantly elevated (48 and 20%, respectively) in copper-deficient rats, indicating that copper deficiency stimulated the expression of the HO-1 gene. Furthermore, hepatic HO-1 protein content was best described by a regression model that included mitochondrial NADH:cytochrome c reductase and succinate:cytochrome c reductase activities, but not cytochrome c oxidase activity ([R.sup.2] = 0.54, P < 0.02). Hydrogen peroxide is a known inducer of HO-1, and our results suggest that increased mitochondrial [H.sub.2][O.sub.2] production resulting from inhibition of respiratory complex activities contributes to the induction of HO-1 during copper deficiency. The levels of HO-1 protein and mRNA were also elevated (85 and 95%, respectively) in hearts from copper-deficient rats, indicating that the effects of copper deficiency on HO-1 gene expression are not limited to hepatic tissue. J. Nutr. 134: 1328-1333, 2004. KEY WORDS: * heme oxygenase * mitochondria * hydrogen peroxide * respiratory complexes * copper deficiency

Previous studies have show that changes in protein kinase C (PKC) isoform expression may be related to increased susceptibility of copper-deficient rats to aberrant crypt formation. The purpose of this study was to determine whether dietary copper would affect azoxymethane-induced intestinal tumor formation and PKC isozyme expression in normal colonic mucosa and tumor samples. Eighty weanling Fischer-344 rats were randomly assigned to diets that contained either 0.8 or 5.3 [micro]g Cu/g diet. After 24 and 31 d of diet consumption, 30 rats/diet were administered azoxymethane (15 mg/kg i.p.) and 10 rats/diet were administered saline. Rats continued to consume their respective diets for an additional 38 wk. Rats injected with azoxymethane and fed the low copper diet had a significantly (P < 0.0001) greater small intestinal and total tumor incidence compared with rats fed adequate dietary copper. However, dietary copper did not affect colon tumor incidence. Low dietary copper significantly (P < 0.004) decreased PKC [alpha] protein expression in normal but not in tumor tissue. In contrast, low dietary copper did not affect PKC [delta] or [zeta] protein expression in either the normal or tumor tissue. PKC [alpha] and [delta] protein and mRNA expression were lower in tumor tissue than in normal tissue. These results along with previous observations suggest that dietary copper-mediated changes in PKC [alpha], [delta] and [zeta] protein expression are not as important for colon tumor promotion/progression as they are for tumor initiation. J. Nutr. 132: 1018-1025, 2002. KEY WORDS: * colon cancer * protein kinase C * copper * rats

Abstract Background Immune modulation by parasites may influence susceptibility to bacteria and viruses. We examined the association between current parasite infections, HIV and syphilis (measured in blood or stool samples using standard methods) and antibodies against Kaposi's sarcoma herpesvirus (KSHV), measured by ELISA, in 1915 stored plasma samples from pregnant women in Entebbe, Uganda. Results Seroprevalence of KSHV was higher in women with malaria parasitaemia (73% vs 60% p = 0.01), hookworm (67% vs 56% p = 0.001) and Mansonella perstans (69% vs 59% p = 0.05); seroprevalence increased with increasing intensity of hookworm infection (p < 0.001[trend]). No associations were found for HIV, five other parasites or active syphilis. These effects were not explained by socioeconomic status or education. Conclusions Specific parasite infections are associated with presence of antibodies against KSHV, perhaps mediated via their effect on immune function.

Worldwide, colon cancer is the fourth greatest cause of cancer death. In the United States, it is the second leading cause of cancer mortality. It is believed that diet is [...]

Abstract: Cu deficiency disrupts the architecture of mitochondria, impairs respiration, and inhibits the activity of cytochrome c oxidase — the terminal, Cu-dependent respiratory complex (Complex IV) of the electron transport chain. This suggests that perturbations in the respiratory chain may contribute to the changes in mitochondrial structure caused by Cu deficiency. This study investigates the effect of Cu deficiency on Ca2+-induced mitochondrial swelling as it relates to changes in respiratory complex activities in cardiac mitochondria of rats. Male weanling rats were fed diets containing either no added Cu (Cu0), 1.5 mg Cu/kg (Cu1.5), 3 mg Cu/kg (Cu3) or 6 mg Cu/kg (Cu6). The rate of Ca2+-induced mitochondrial swelling in the presence of succinate and oligomycin was reduced, and the time to reach maximal swelling was increased only in the rats consuming Cu0 diet. Cytochrome c oxidase activity was reduced 60% and 30% in rats fed Cu0 and Cu1.5, respectively, while NADH:cytochrome c reductase (Complex I+ComplexIII) activity was reduced 30% in rats consuming both Cu0 and Cu1.5. Mitochondrial swelling is representative of mitochondrial permeability transition pore (MPTP) formation and the results suggest that Ca2+-induced MPTP formation occurs in cardiac mitochondria of Cu-deficient rats only when cytochrome c oxidase activity falls below 30% of normal. Decreased respiratory complex activities caused by severe Cu deficiency may inhibit MPTP formation by increasing matrix ADP concentration or promoting oxidative modifications that reduce the sensitivity of the calcium trigger for MPTP formation. [Copyright &y& Elsevier]