Joseph Rudinger memorial lecture: Unexpected functions of angiotensin converting enzyme, beyond its enzymatic activity

Martinez, Jean

doi:10.1002/psc.3022

Cited by 2 publications

(1 citation statement)

References 66 publications

(76 reference statements)

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“…Acein, a nonapeptide of sequence H-Pro-Pro-Thr-Thr-Thr-Lys-Phe-Ala-Ala-OH stimulates dopamine release in the brain [ 13 ] by binding with high affinity to the striatal bound-membrane angiotensin converting enzyme (ACE) of rodents [ 13 , 14 ]. Further structure-activity relationship studies revealed that the C-terminal pentapeptide of Acein H-Thr-Lys-Phe-Ala-Ala-OH is the smallest fragment exhibiting full biological activity [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

The peptide Acein promotes dopamine secretion through clec-126 to extend the lifespan of elderly C. elegans

Wang,

Setrerrahmane

et al. 2023

Aging

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Dopamine plays a crucial role in regulating brain activity and movement and modulating human behavior, cognition and mood. Regulating dopamine signaling may improve cognitive abilities and physical functions during aging. Acein, a nonapeptide of sequence H-Pro-Pro-Thr-Thr-Thr-Lys-Phe-Ala-Ala-OH is able to stimulate dopamine secretion in the brain. By using genetic editing and lifespan investigation in C. elegans , we showed that the lack of the C-type lectin domain-containing protein clec-126 significantly suppressed the aging phenotype and prolonged lifespan, while overexpression of clec-126 promoted aging-related phenotypes and accelerated the aging process. We examined the aging phenotype of C. elegans and showed that Acein could induce a decrease in clec-126 expression, prolonging the lifespan of aged C. elegans . The mechanism proceeds through the Acein-induced stimulation of dopamine secretion that ameliorates motor function decline and extends the healthy lifespan of aged C. elegans . In addition, we also observed an increase in brood number. Our study has shown that Acein regulates dopamine secretion and has good antiaging activity by decreasing clec-126 expression.

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Section: Introductionmentioning

confidence: 99%

The peptide Acein promotes dopamine secretion through clec-126 to extend the lifespan of elderly C. elegans

Wang,

Setrerrahmane

et al. 2023

Aging

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The C-terminal pentapeptide acein analogue (JMV3315) stimulates dopamine release in the brain

Lucas-Valmalle,

Subra,

Verdié

et al. 2023

Aust. J. Chem.

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We have previously reported the synthesis and biological activity of a newly identified peptide of sequence H–Pro–Pro–Thr–Thr–Thr–Lys–Phe–Ala–Ala–OH called acein that is able to stimulate dopamine release in the brain of rodents in vivo and ex vivo by interacting with angiotensin converting enzyme (ACE). In the present piece of work, we studied the structure–activity relationships of acein using displacement experiments of the labelled ligand [125I]Tyr–Pro–Pro–Thr–Thr–Thr–Lys–Phe–Ala–Ala–OH on guinea pig brain membranes, known to have high-affinity acein binding sites. We determined that the C-terminal pentapeptide H–Thr–Lys–Phe–Ala–Ala–OH is the minimal structure able to interact with high affinity (Ki (inhibitory constant) 13 ± 2 nM) with acein binding sites. Among the analogues of the pentapeptide that were synthesized, the pentapeptide H–Thr–Lys–Tyr–Ala–Ala–OH showed the highest affinity (Ki 3.7 ± 1.0 nM). Accordingly, this pentapeptide was able to stimulate dopamine release from striatal slices taken from the sensorimotor territory of rats.

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Joseph Rudinger memorial lecture: Unexpected functions of angiotensin converting enzyme, beyond its enzymatic activity

Cited by 2 publications

References 66 publications

The peptide Acein promotes dopamine secretion through clec-126 to extend the lifespan of elderly C. elegans

The peptide Acein promotes dopamine secretion through clec-126 to extend the lifespan of elderly C. elegans

The C-terminal pentapeptide acein analogue (JMV3315) stimulates dopamine release in the brain

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