{Reference Type}: Journal Article
{Title}: Altered VDAC-HK association and apoptosis in mouse peripheral blood lymphocytes exposed to diabetic condition: an in vitro and in vivo study.
{Author}: Sohlang MN;Majaw S;
{Journal}: Arch Physiol Biochem
{Volume}: 129
{Issue}: 3
{Year}: Jun 2023 12
{Factor}: 3.188
{DOI}: 10.1080/13813455.2020.1867187
{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.