Altered VDAC-HK association and apoptosis in mouse peripheral blood lymphocytes exposed to diabetic condition: an in vitro and in vivo study

Abstract

Increased apoptotic lymphocytes have been correlated to a high incidence of infection in poorly controlled diabetes. This study aimed to determine whether altered voltage-dependent anion channel (VDAC)-hexokinase (HK) association contributes to the increase in apoptosis. Mouse peripheral blood lymphocytes (PBL) exposed to high glucose (Glc)/palmitic acid (PA) were used as the in vitro model, which was compared with PBL isolated from alloxan-induced diabetic mice (in vivo model). Our results showed a significant increase in apoptosis as indicated by the apoptotic index, caspase-3 activity, mitochondrial membrane potential and ultrastructural study. HK and glucose-6-phosphate dehydrogenase (G6PDH) activities were markedly reduced with a profound increase in glucose-6-phosphate level. Co-immunoprecipitation confirms HK interaction with VDAC, an outer mitochondrial membrane protein. Inhibited glycolytic enzyme, i.e. HK and reduced HK-VDAC interaction in our study could contribute to increased apoptosis in lymphocytes exposed to high Glc/PA. Targeting HK-VDAC interaction may therefore provide therapeutic potential for the treatment of diabetes-associated infection.

Keywords:

• Apoptosis
• diabetes
• hexokinase
• peripheral blood lymphocytes
• voltage-dependent anion channel

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Acknowledgement

Authors are grateful to Prof. Tapas K. Choudhuri, Retired Professor, Dept. of Zoology, University of North Bengal, Adjunct Professor, Dept. of Biotechnology, Brainware University for his valuable insights.

Compliance with ethical standards

This article does not contain any studies involving human participants performed by any of the authors. The handling of animals and experimentations are per the Institutional Ethics Committee (Animal Models) of North-Eastern Hill University, Shillong, Meghalaya, India.

Disclosure statement

The authors declare that they have no conflicts of interest.

Data availability statement

The data included in this study are available with the authors and may be provided upon reasonable request.

Additional information

Funding

The research was supported by the Department of Biotechnology & Bioinformatics, North-Eastern Hill University through the various grants received by the department: UGC-Non-plan (FA2/NP/Allocation/2018–19 dated 13.08.2018), UGC-SAP (F4-7/2016/DRS-I (SAP-II) dated 28.04.2016), DBT-M.Sc. Teaching Program (102/IFD/DBT/SAN/2140/2006–07 dated 16.03.2017), DST-FIST (SR/FSI/LSI-666/2016(C) dated 15.12.2017). The author, Melinda Nongbet Sohlang is also thankful to the Department of Biotechnology, Government of India, New Delhi for providing the DBT-JRF fellowship.