The elusive physiologic role of Factor XII

Abstract Histidine-rich glycoprotein (HRG) circulates in plasma at a concentration of 2μM and binds plasminogen, fibrinogen, and thrombospondin. Despite these interactions, the physiologic role of HRG is unknown. Previous studies have shown that mice and humans deficient in HRG have shortened plasma clotting times. To better understand this phenomenon, we examined the effect of HRG on clotting tests. HRG prolongs the activated partial thromboplastin time in a concentration-dependent fashion but has no effect on tissue factor–induced clotting, localizing its effect to the contact pathway. Plasma immunodepleted of HRG exhibits a shortened activated partial thromboplastin time that is restored to baseline with HRG replenishment. To explore how HRG affects the contact pathway, we examined its binding to factors XII, XIIa, XI, and XIa. HRG binds factor XIIa with high affinity, an interaction that is enhanced in the presence of Zn2+, but does not bind factors XII, XI, or XIa. In addition, HRG inhibits autoactivation of factor XII and factor XIIa–mediated activation of factor XI. These results suggest that, by binding to factor XIIa, HRG modulates the intrinsic pathway of coagulation, particularly in the vicinity of a thrombus where platelet release of HRG and Zn2+ will promote this interaction.

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Deconjugation of bilirubin-IX alpha glucuronides: a physiologic role of hepatic microsomal beta-glucuronidase.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)49447-7 ◽

1993 ◽

Vol 268 (31) ◽

pp. 23197-23201

Author(s):

J.F. Whiting ◽

J.P. Narciso ◽

V Chapman ◽

B.J. Ransil ◽

R.T. Swank ◽

...

Keyword(s):

Physiologic Role

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Protein Synthesis in Human Leukocytes and Lymphocytes: 1. Effect of Steroids and Sterols

Blood ◽

10.1182/blood.v34.3.348.348 ◽

1969 ◽

Vol 34 (3) ◽

pp. 348-356 ◽

Cited By ~ 18

Author(s):

SEYMOUR WERTHAMER ◽

CARL HICKS ◽

LEONARD AMARAL

Keyword(s):

Protein Synthesis ◽

Steroid Hormones ◽

Plasma Protein ◽

Human Lymphocytes ◽

Amino Acid Incorporation ◽

Binding Factor ◽

In Vitro Effects ◽

Physiologic Role

Abstract The in vitro effects of sterols, cholesterol and 3-methyl cholanthrene and steroids, cortisol, prednisolone and testosterone on protein synthesis in separate popultions of human lymphocytes and leukocytes has been investigated. It has been shown that all agents used result in the inhibition of protein synthesis under these conditions. It has also been shown that the inhibitory mechanism of the steroid hormones requires the presence of plasma, presumably as a protein binding factor in order to achieve its effect. The sterol, cholesterol and 3-methyl cholanthrene, in the absence of plasma, still inhibit amino acid incorporation. However, in the case of cholesterol, the magnitude of inhibition is lower than that observed in the presence of plasma, perhaps indicating a partial plasma dependence. The results presented therefore support the hypothesis that the inhibition of lymphocyte protein synthesis by steroid hormones occurs only when the steroid is bound to a plasma protein. The physiologic role of the plasma protein-cortisol complex and its relation to the condition of lymphopenia in man is discussed.

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Physiologic Role of ETA Receptors in the Regulation of Renal Hemodynamics in Normal and Salt-Depleted Rats

Journal of Cardiovascular Pharmacology ◽

10.1097/00005344-199506263-00137 ◽

1995 ◽

Vol 26 ◽

pp. S466-469 ◽

Cited By ~ 3

Author(s):

Clarice Kazue Fujihara ◽

Gilberto De Nucci ◽

Roberto Zatz

Keyword(s):

Renal Hemodynamics ◽

Physiologic Role

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Differential Steroid Secretion and Gonadotropin Response by Individual Tertiary Porcine Follicles in Vitro. Possible Physiologic Role of Atretic Follicles1

Biology of Reproduction ◽

10.1095/biolreprod44.3.461 ◽

1991 ◽

Vol 44 (3) ◽

pp. 461-468 ◽

Cited By ~ 6

Author(s):

Gregor Westhof ◽

Karin F. Westhof ◽

Wilhelm L. Braendle ◽

Gere S. diZerega

Keyword(s):

Steroid Secretion ◽

Physiologic Role

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Generation of a Mouse Model for Arginase II Deficiency by Targeted Disruption of the Arginase II Gene

Molecular and Cellular Biology ◽

10.1128/mcb.21.3.811-813.2001 ◽

2001 ◽

Vol 21 (3) ◽

pp. 811-813 ◽

Cited By ~ 93

Author(s):

Ou Shi ◽

Sidney M. Morris ◽

Huda Zoghbi ◽

Carl W. Porter ◽

William E. O'Brien

Keyword(s):

Urea Cycle ◽

Elevated Plasma ◽

Wild Type ◽

Targeted Disruption ◽

Arginase Ii ◽

Plasma Arginine ◽

Physiologic Role ◽

Deficient Mice ◽

Arginase I

ABSTRACT Mammals express two isoforms of arginase, designated types I and II. Arginase I is a component of the urea cycle, and inherited defects in arginase I have deleterious consequences in humans. In contrast, the physiologic role of arginase II has not been defined, and no deficiencies in arginase II have been identified in humans. Mice with a disruption in the arginase II gene were created to investigate the role of this enzyme. Homozygous arginase II-deficient mice were viable and apparently indistinguishable from wild-type mice, except for an elevated plasma arginine level which indicates that arginase II plays an important role in arginine homeostasis.

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DLK1 Expressed in Mouse Orexin Neurons Modulates Anxio-Depressive Behavior but Not Energy Balance

Brain Sciences ◽

10.3390/brainsci10120975 ◽

2020 ◽

Vol 10 (12) ◽

pp. 975

Author(s):

Tatiyana Harris ◽

Raluca Bugescu ◽

Jaylyn Kelly ◽

Anna Makela ◽

Morgan Sotzen ◽

...

Keyword(s):

Body Weight ◽

Energy Balance ◽

Ingestive Behavior ◽

Hypothalamic Area ◽

Disease States ◽

Adult Mice ◽

Plus Maze ◽

And Behavior ◽

Physiologic Role

Lateral hypothalamic area (LHA) neurons expressing the neuropeptide orexin (OX) are implicated in obesity and anxio-depression. However, these neurons release OX as well as a host of other proteins that might contribute to normal physiology and disease states. We hypothesized that delta-like homolog 1 (DLK1), a protein reported to be co-expressed by all OX neurons, contributes to the regulation of energy balance and/or anxio-depression. Consistent with previous reports, we found that all rat OX neurons co-express DLK1. Yet, in mice and humans only a subset of OX neurons co-expressed DLK1. Since human OX-DLK1 distribution is more similar to mice than rats, mice are a comparable model to assess the human physiologic role of DLK1. We therefore used a viral lesion strategy to selectively delete DLK1 within the LHA of adult mice (DLK1Null) to reveal its role in body weight and behavior. Adult-onset DLK1 deletion had no impact on body weight or ingestive behavior. However, DLK1Null mice engaged in more locomotor activity than control mice and had decreased anxiety and depression measured via the elevated plus maze and forced swim tests. These data suggest that DLK1 expression via DLK1-expressing OX neurons primarily contributes to anxio-depression behaviors without impacting body weight.

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