THE INTERACTIONS OF PYRROLOQUINOLINE QUINONE AND DIPHENYLENE IODONIUM IN YOUNG MICE.
T. Stites, M. Mitchell, M. Rose, B. Rucker, and R. Rucker Department of Nutrition, University of California, 95616 (1995)
Pyrroloquinoline Quinone (PQQ) has been identified as a potential growth factor in neonatal mice, an antioxidant, a modulator of the N-methyl-D-aspartate receptor redox site in brain tissue, and a potential target for mitochondrial complex I inhibitors, e.g. rotenone or diphenylene iodonium (DPI). The latter is suggested by recent work from Dr. Paul Gallop's group (Children's Hospital, Harvard Univ.). Herein, we report corroboration of such a PQQ X DPI interaction. Weanling mice were fed a chemically-defined diet devoid of PQQ, but given a daily gravage PQQ at 0, 0.4 or 4 �g/g B.W. At each PQQ level, DPI was injected i.p. at either 0, 0.8 or 1.6 �g/g B.W. After 4 weeks of treatment, mice given >0.4 �g/g DPI and 0 �g/g PQQ lost ~2-3 g B.W. Mice in this group also had significantly lower plasma glucose levels. At PQQ levels of >0.4 mg/g, no weight loss or hypoglycemia was observed in any of the groups. The different routes of delivery were chosen to preclude direct obvious chemical interactions. The goal at this point is to better define the mechanism for the interaction. Supported by funds from the USDA
Abstract #2
DIETARY DEFICIENCY OF PYRROLOQUINOLINE QUINONE (PQQ) ALTERS MITOCHONDRIAL FUNCTION IN YOUNG MICE.
T.E. Stites, J. Mah, R. Fl�ckiger, M. Paz, P. Gallop, and R. Rucker
Department of Nutrition, University of California, Davis, CA.
Lab of Human Biochemistry, Children's Hospital Boston, MA.(1996)
PQQ has been proposed as a cofactor in eukaryotes based on evidence that 1) its absence impairs growth in mice and upon dietary supplementation in nanomolar quantities it restores normal growth and development (J Nutr: 124: 744), and 2) is found in common foods (Biochem J:307:331). We have also provided evidence that PQQ-like compounds are present in mitochondria (BBRC:196:61). Our hypothesis is that PQQ deficiency impairs mitochondrial function. Balb/c pups born from dams fed purified amino acid based diets lacking PQQ (PQQ(-) and diets with supplemental PQQ added at 10 mg/kg diet (PQQ(+)) were examined at 3.5 weeks of age. The PQQ(-) mice ranged in weight from 5.7 to 12.7 g (mean = 9.9) and PQQ(+) mice ranged from 9.1 to 17.0 g (mean = 13.9). The respiratory control ratio (RCR) and P:O ratio were assessed on isolated liver mitochondria. Parameters of respiration were difficult to obtain from PQQ(-) mice. The average RCR for the PQQ(-) was 2.15 compared to 2.47 for PQQ(+) mice. There were no significant differences in the P:O ratio between groups. The values for RCR were positively correlated with body weight (r2=0.45). Based on these results we are investigating whether the inability to obtain successful RCR estimates in PQQ(-) mice is due to defects in mitochondria structure or size, or alternatively a methodological issue associated with the difference in body weight. Nevertheless, the data provide evidence for impaired mitochondrial function in PQQ(-) mice.
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Pyrroloquinoline Quinone (PQQ) has been identified as a potential growth factor in neonatal mice, an antioxidant, a modulator of the N-methyl-D-aspartate receptor redox site in brain tissue, and a potential target for mitochondrial complex I inhibitors, e.g. rotenone or diphenylene iodonium (DPI). The latter is suggested by recent work from Dr. Paul Gallop's group (Children's Hospital, Harvard Univ.). Herein, we report corroboration of such a PQQ X DPI interaction. Weanling mice were fed a chemically-defined diet devoid of PQQ, but given a daily gravage PQQ at 0, 0.4 or 4 �g/g B.W. At each PQQ level, DPI was injected i.p. at either 0, 0.8 or 1.6 �g/g B.W. After 4 weeks of treatment, mice given >0.4 �g/g DPI and 0 �g/g PQQ lost ~2-3 g B.W. Mice in this group also had significantly lower plasma glucose levels. At PQQ levels of >0.4 mg/g, no weight loss or hypoglycemia was observed in any of the groups. The different routes of delivery were chosen to preclude direct obvious chemical interactions. The goal at this point is to better define the mechanism for the interaction. Supported by funds from the USDA
Abstract #2
DIETARY DEFICIENCY OF PYRROLOQUINOLINE QUINONE (PQQ) ALTERS MITOCHONDRIAL FUNCTION IN YOUNG MICE.
T.E. Stites, J. Mah, R. Fl�ckiger, M. Paz, P. Gallop, and R. Rucker
Department of Nutrition, University of California, Davis, CA.
Lab of Human Biochemistry, Children's Hospital Boston, MA.(1996)
PQQ has been proposed as a cofactor in eukaryotes based on evidence that 1) its absence impairs growth in mice and upon dietary supplementation in nanomolar quantities it restores normal growth and development (J Nutr: 124: 744), and 2) is found in common foods (Biochem J:307:331). We have also provided evidence that PQQ-like compounds are present in mitochondria (BBRC:196:61). Our hypothesis is that PQQ deficiency impairs mitochondrial function. Balb/c pups born from dams fed purified amino acid based diets lacking PQQ (PQQ(-) and diets with supplemental PQQ added at 10 mg/kg diet (PQQ(+)) were examined at 3.5 weeks of age. The PQQ(-) mice ranged in weight from 5.7 to 12.7 g (mean = 9.9) and PQQ(+) mice ranged from 9.1 to 17.0 g (mean = 13.9). The respiratory control ratio (RCR) and P:O ratio were assessed on isolated liver mitochondria. Parameters of respiration were difficult to obtain from PQQ(-) mice. The average RCR for the PQQ(-) was 2.15 compared to 2.47 for PQQ(+) mice. There were no significant differences in the P:O ratio between groups. The values for RCR were positively correlated with body weight (r2=0.45). Based on these results we are investigating whether the inability to obtain successful RCR estimates in PQQ(-) mice is due to defects in mitochondria structure or size, or alternatively a methodological issue associated with the difference in body weight. Nevertheless, the data provide evidence for impaired mitochondrial function in PQQ(-) mice.
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DIETARY DEFICIENCY OF PYRROLOQUINOLINE QUINONE (PQQ) ALTERS MITOCHONDRIAL FUNCTION IN YOUNG MICE.
T.E. Stites, J. Mah, R. Fl�ckiger, M. Paz, P. Gallop, and R. Rucker
Department of Nutrition, University of California, Davis, CA.
Lab of Human Biochemistry, Children's Hospital Boston, MA.(1996)
PQQ has been proposed as a cofactor in eukaryotes based on evidence that 1) its absence impairs growth in mice and upon dietary supplementation in nanomolar quantities it restores normal growth and development (J Nutr: 124: 744), and 2) is found in common foods (Biochem J:307:331). We have also provided evidence that PQQ-like compounds are present in mitochondria (BBRC:196:61). Our hypothesis is that PQQ deficiency impairs mitochondrial function. Balb/c pups born from dams fed purified amino acid based diets lacking PQQ (PQQ(-) and diets with supplemental PQQ added at 10 mg/kg diet (PQQ(+)) were examined at 3.5 weeks of age. The PQQ(-) mice ranged in weight from 5.7 to 12.7 g (mean = 9.9) and PQQ(+) mice ranged from 9.1 to 17.0 g (mean = 13.9). The respiratory control ratio (RCR) and P:O ratio were assessed on isolated liver mitochondria. Parameters of respiration were difficult to obtain from PQQ(-) mice. The average RCR for the PQQ(-) was 2.15 compared to 2.47 for PQQ(+) mice. There were no significant differences in the P:O ratio between groups. The values for RCR were positively correlated with body weight (r2=0.45). Based on these results we are investigating whether the inability to obtain successful RCR estimates in PQQ(-) mice is due to defects in mitochondria structure or size, or alternatively a methodological issue associated with the difference in body weight. Nevertheless, the data provide evidence for impaired mitochondrial function in PQQ(-) mice.
Go To Home<