Impairment of mitochondrial-nuclear cross talk in neutrophils of patients with type 2 diabetes mellitus.
Increased leukocyte apoptosis is intrinsically linked to disease patho-physiology, susceptibility to and severity of infections in type 2 diabetes mellitus (T2DM) patients. A consistent defect in neutrophil function is considered central to this increased risk for infections. Although redox imbalance is considered a potential mediator of these associated complications, detailed molecular evidence in clinical samples remains largely undetected. The study consisted of three groups (n = 50 each) of Asian Indians: early diagnosed diabetic patients, cases with late-onset diabetic complications and age and gender-matched healthy controls. We evaluated mitochondrial oxidative stress, levels of nuclear DNA damage and apoptosis in peripheral blood neutrophils isolated from T2DM patients. We observed that in both early and late diabetic subjects, the HbA1c levels in neutrophils were altered considerably with respect to healthy controls. Increased oxidative stress observed in both early and late diabetics imply the disentanglement of fine equilibrium of mitochondria-nuclear cross talk which eventually effected the augmentation of downstream nuclear γH2AX activation and caspase-3 expression. It would be overly naïve to refute the fact that mitochondrial deregulation in neutrophils perturbs immunological balance in type 2 diabetic conditions. By virtue of our data, we posit that maneuvering mitochondrial function might offer a prospective and viable method to modulate neutrophil function in T2DM. Nevertheless, similar investigations from other ethnic groups in conjunction with experimental evidences would be a preeminent need. Obviously, our study might aid to comprehend this complex interplay between mitochondrial dysfunction and neutrophil homeostasis in T2DM.
Department of Biotechnology, Dr. HS Gour Central University, Sagar, India ; Department of Research, Bhopal Memorial Hospital & Research Centre, Bhopal, India.
Saba
S
Khan
Department of Biotechnology, Dr. HS Gour Central University, Sagar, India ; Department of Research, Bhopal Memorial Hospital & Research Centre, Bhopal, India ; Division of Translational Research, Tata Memorial Centre, ACTREC, Navi Mumbai, 410 210 India.
Gorantla V
GV
Raghuram
Department of Research, Bhopal Memorial Hospital & Research Centre, Bhopal, India.
Neelam
N
Pathak
Department of Biotechnology, Dr. HS Gour Central University, Sagar, India.
Subodh K
SK
Jain
Department of Research, Bhopal Memorial Hospital & Research Centre, Bhopal, India.
Dolly H
DH
Chandra
Department of Research, Bhopal Memorial Hospital & Research Centre, Bhopal, India ; Division of Translational Research, Tata Memorial Centre, ACTREC, Navi Mumbai, 410 210 India.
Pradyumna K
PK
Mishra
Free radical injury; Mitochondria dysfunction; Translational research; Type 2 diabetes mellitus