An intact C-terminal end of albumin is required for its long half-life in humans

Nilsen, Jeannette; Trabjerg, Esben; Grevys, Algirdas; Azevedo, Cláudia; Brennan, Stephen O.; Stensland, Maria; Wilson, John James; Sand, Kine Marita Knudsen; Bern, Malin C.; Dalhus, Bjørn; Roopenian, Derry C.; Sandlie, Inger; Rand, Kasper D.; Andersen, Jan Terje

doi:10.1038/s42003-020-0903-7

Cited by 50 publications

(30 citation statements)

References 71 publications

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“…Last, we established the 24-hour concentration profiles of SHBG and albumin and observed a low-amplitude circadian rhythm in albumin levels with higher levels during the day compared to nighttime. Albumin has a half-life of circa 3 weeks and is not dependent on nutritional status, so this cannot explain the moderate circadian rhythm in albumin levels [ 67 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

Relationships Between 24-hour LH and Testosterone Concentrations and With Other Pituitary Hormones in Healthy Older Men

Spoel

Roelfsema

Heemst

2021

Journal of the Endocrine Society

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Objective To investigate the relationship between LH and T, which characteristics associate with the strength of this relationship, and their interrelationships with GH, TSH, cortisol, and ACTH. Design Hormones were measured in serum samples collected every 10 min during 24 h from 20 healthy men, comprising 10 offspring of long-lived families and 10 control subjects, with a mean (SD) age of 65.6 (5.3) years. We performed cross-correlation analyses to assess the relative strength between two timeseries for all possible time shifts. Results Mean (95% CI) maximal correlation was 0.21 (0.10–0.31) at lag time 60 min between LH and total T concentrations. Results were comparable for calculated free, bioavailable, or secretion rates of T. Men with strong LH-T cross-correlations had, compared to men with no cross-correlation, lower fat mass (18.5 (14.9–19.7) vs. 22.3 (18.4–29.4) kg), waist circumference (93.6 (5.7) vs. 103.1 (12.0) cm), hsCRP (0.7 (0.4–1.3) vs. 1.8 (0.8–12.3) mg/L), IL-6 (0.8 (0.6–1.0) vs. 1.2 (0.9–3.0) pg/mL), and 24-h mean LH (4.3 (2.0) vs. 6.1 (1.5) U/L), and stronger LH-T feedforward synchrony (1.5 (0.3) vs. 1.9 (0.2)). Furthermore, T was positively cross-correlated with TSH (0.32 (0.21–0.43)), cortisol (0.26 (0.19–0.33)), and ACTH (0.26 (0.19–0.32)). Conclusions LH is followed by T with a delay of 60 min in healthy older men. Men with a strong LH-T relationship had more favorable body composition, inflammatory markers, LH levels, and LH-T feedforward synchrony. We observed positive correlations between T and TSH, cortisol, and ACTH.

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Section: Discussionmentioning

confidence: 99%

Relationships Between 24-hour LH and Testosterone Concentrations and With Other Pituitary Hormones in Healthy Older Men

Spoel

Roelfsema

Heemst

2021

Journal of the Endocrine Society

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“…The absorbance was measured at 450 nm with a microplate reader (Molecular Devices). The plasma AXNA2 half-life was calculated using the following formula as described previously [ 17 ]: t 1/2 = log 0.5/(log Ae/A0) × t , where t 1/2 is the half-life, Ae is the amount of AXNA2 remaining, A0 is the amount of AXNA2 on 2 h, and t is the elapsed time.…”

Section: Methodsmentioning

confidence: 99%

Recombinant annexin A2 inhibits peripheral leukocyte activation and brain infiltration after traumatic brain injury

Liu

Han

et al. 2021

J Neuroinflammation

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Background Traumatic brain injury (TBI) is a significant cause of death and disability worldwide. The TLR4-NFκB signaling cascade is the critical pro-inflammatory activation pathway of leukocytes after TBI, and modulating this signaling cascade may be an effective therapeutic target for treating TBI. Previous studies indicate that recombinant annexin A2 (rA2) might be an interactive molecule modulating the TLR4-NFκB signaling; however, the role of rA2 in regulating this signaling pathway in leukocytes after TBI and its subsequent effects have not been investigated. Methods C57BL/6 mice were subjected to TBI and randomly divided into groups that received intraperitoneal rA2 or vehicle at 2 h after TBI. The peripheral leukocyte activation and infiltrating immune cells were examined by flow cytometry, RT-qPCR, and immunostaining. The neutrophilic TLR4 expression on the cell membrane was examined by flow cytometry and confocal microscope, and the interaction of annexin A2 with TLR4 was assessed by co-immunoprecipitation coupled with Western blotting. Neuroinflammation was measured via cytokine proteome profiler array and RT-qPCR. Neurodegeneration was determined by Western blotting and immunostaining. Neurobehavioral assessments were used to monitor motor and cognitive function. Brain tissue loss was assessed via MAP2 staining. Results rA2 administration given at 2 h after TBI significantly attenuates neutrophil activation and brain infiltration at 24 h of TBI. In vivo and in vitro data show that rA2 binds to and reduces TLR4 expression on the neutrophil surface and suppresses TLR4/NFκB signaling pathway in neutrophils at 12 h after TBI. Furthermore, rA2 administration also reduces pro-inflammation of brain tissues within 24 h and neurodegeneration at 48 h after TBI. Lastly, rA2 improves long-term sensorimotor ability and cognitive function, and reduces brain tissue loss at 28 days after TBI. Conclusions Systematic rA2 administration at 2 h after TBI significantly inhibits activation and brain infiltration of peripheral leukocytes, especially neutrophils at the acute phase. Consequently, rA2 reduces the detrimental brain pro-inflammation-associated neurodegeneration and ultimately ameliorates neurological deficits after TBI. The underlying molecular mechanism might be at least in part attributed to rA2 bindings to pro-inflammatory receptor TLR4 in peripheral leukocytes, thereby blocking NFκB signaling activation pathways following TBI.

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“…The absorbance was measured at 450 nm with a microplate reader (Molecular Devices). The plasma ANXA2 half-life was calculated using the following the formula as described previously ( Nilsen et al, 2020 ): t 1/2 = log 0.5/(log Ae/A0)× t, where t 1/2 is the half-life, Ae is the amount of ANXA2 remaining, A0 is the amount of ANXA2 on 2 h, and t is the elapsed time.…”

Section: Methodsmentioning

confidence: 99%

Recombinant Annexin A2 Administration Improves Neurological Outcomes After Traumatic Brain Injury in Mice

et al. 2021

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Microvascular failure is one of the key pathogenic factors in the dynamic pathological evolution after traumatic brain injury (TBI). Our laboratory and others previously reported that Annexin A2 functions in blood-brain barrier (BBB) development and cerebral angiogenesis, and recombinant human Annexin A2 (rA2) protected against hypoxia plus IL-1β-induced cerebral trans-endothelial permeability in vitro, and cerebral angiogenesis impairment of AXNA2 knock-out mice in vivo. We thereby hypothesized that ANXA2 might be a cerebrovascular therapy candidate that targets early BBB integrity disruption, and subacute/delayed cerebrovascular remodeling after TBI, ultimately improve neurological outcomes. In a controlled cortex impact (CCI) mice model, we found rA2 treatment (1 mg/kg) significantly reduced early BBB disruption at 24 h after TBI; and rA2 daily treatment for 7 days augmented TBI-induced mRNA levels of pro-angiogenic and endothelial-derived trophic factors in cerebral microvessels. In cultured human brain microvascular endothelial cells (HBMEC), through MAPKs array, we identified that rA2 significantly activated Akt, ERK, and CREB, and the activated CREB might be responsible for the rA2-induced VEGF and BDNF expression. Moreover, rA2 administration significantly increased cerebral angiogenesis examined at 14 days and vessel density at 28 days after TBI in mice. Consistently, our results validated that rA2 significantly induced angiogenesis in vitro, evidenced by tube formation and scratched migration assays in HBMEC. Lastly, we demonstrated that rA2 improved long-term sensorimotor and cognitive function, and reduced brain tissue loss at 28 days after TBI. Our findings suggest that rA2 might be a novel vascular targeting approach for treating TBI.

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An intact C-terminal end of albumin is required for its long half-life in humans

Cited by 50 publications

References 71 publications

Relationships Between 24-hour LH and Testosterone Concentrations and With Other Pituitary Hormones in Healthy Older Men

Relationships Between 24-hour LH and Testosterone Concentrations and With Other Pituitary Hormones in Healthy Older Men

Recombinant annexin A2 inhibits peripheral leukocyte activation and brain infiltration after traumatic brain injury

Recombinant Annexin A2 Administration Improves Neurological Outcomes After Traumatic Brain Injury in Mice

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