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Chimeric Agonist of Galanin Receptor GALR2 Reduces Heart Damage in Rats with Streptozotocin-Induced Diabetes

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Abstract

Neuropeptide galanin and its N-terminal fragments reduce the generation of reactive oxygen species and normalize metabolic and antioxidant states of myocardium in experimental cardiomyopathy and ischemia/reperfusion injury. The aim of this study was to elucidate the effect of WTLNSAGYLLGPβAH-OH (peptide G), a pharmacological agonist of the galanin receptor GalR2, on the cardiac injury induced by administration of streptozotocin (STZ) in rats. Peptide G was prepared by solid phase peptide synthesis using the Fmoc strategy and purified by preparative HPLC; its structure was confirmed by 1H-NMR spectroscopy and MALDI-TOF mass spectrometry. Experimental animals were randomly distributed into five groups: C, control; S, STZ-treated; SG10, STZ + peptide G (10 nmol/kg/day); SG50, STZ + peptide G (50 nmol/kg/day); G, peptide G (50 nmol/kg/day). Administration of peptide G prevented hyperglycemia in SG50 rats. By the end of the experiment, the ATP content, total pool of adenine nucleotides, phosphocreatine (PCr) content, and PCr/ATP ratio in the myocardium of animals of the SG50 group were significantly higher than in rats of the S group. In the SG50 and SG10 groups, the content of lactate and lactate/pyruvate ratio in the myocardium were reduced, while the glucose content was increased vs. the S group. Both doses of peptide G reduced the activation of creatine kinase-MB and lactate dehydrogenase, as well as the concentration of thiobarbituric acid reactive products in the blood plasma of STZ-treated rats to the control values. Taken together, these results suggest that peptide G has cardioprotective properties in type 1 diabetes mellitus. Possible mechanisms of peptide G action in the STZ-induced diabetes are discussed.

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Abbreviations

ΣAN:

total pool of adenine nucleotides (ATP + ADP + AMP)

ΣCr:

total creatine (PCr + Cr)

CK-MB:

creatine kinase MB

DM:

diabetes mellitus

GLUT4:

glucose transporter 4

LDH:

lactate dehydrogenase

LPO:

lipid peroxidation

PCr:

phosphocreatine

ROS:

reactive oxygen species

STZ:

streptozotocin

TBARS:

2-tiobarbituric acid reactive substances

WTLNSAGYLL-NH2:

N-terminal fragment of galanin 2-11

WTLNSAGYLLGPHA-OH:

N-terminal fragment of galanin 2-15

WTLNSAGYLLGPβAH-OH (G):

modified analog of galanin 2-15

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Funding

The work was supported by the Russian Foundation for Basic Research (projects nos. 18-015-0008-a and 18-015-0009-a) and Ministry of Health of the Russian Federation (registration no. NIOKTR 121031700143-1).

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Authors and Affiliations

  1. National Medical Research Center for Cardiology, 121552, Moscow, Russia

    Irina M. Studneva, Oksana M. Veselova, Igor V. Dobrokhotov, Larisa I. Serebryakova, Marina E. Palkeeva, Alexander S. Molokoedov, Andrey A. Azmuko, Michael V. Ovchinnikov, Maria V. Sidorova & Oleg I. Pisarenko

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  1. Irina M. Studneva
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  2. Oksana M. Veselova
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  3. Igor V. Dobrokhotov
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Correspondence to Oleg I. Pisarenko.

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Studneva, I.M., Veselova, O.M., Dobrokhotov, I.V. et al. Chimeric Agonist of Galanin Receptor GALR2 Reduces Heart Damage in Rats with Streptozotocin-Induced Diabetes. Biochemistry Moscow 87, 346–355 (2022). https://doi.org/10.1134/S0006297922040046

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