Mitochondrial Generated Redox Stress Differently Affects the Endoplasmic Reticulum of Circulating Lymphocytes and Monocytes in Treatment-Naïve Hodgkin’s Lymphoma
Cecilia Marini,
Vanessa Cossu,
Matteo Bauckneht,
Sonia Carta,
Francesco Lanfranchi,
Francesca D’Amico,
Silvia Ravera,
Anna Maria Orengo,
Chiara Ghiggi,
Filippo Ballerini,
Paolo Durando,
Sabrina Chiesa,
Alberto Miceli,
Maria Isabella Donegani,
Silvia Morbelli,
Silvia Bruno,
Gianmario Sambuceti
Affiliations
Cecilia Marini
CNR, Institute of Molecular Bioimaging and Physiology (IBFM), 20054 Milan, Italy
Vanessa Cossu
IRCCS, Ospedale Policlinico San Martino, 16132 Genoa, Italy
Matteo Bauckneht
IRCCS, Ospedale Policlinico San Martino, 16132 Genoa, Italy
Sonia Carta
IRCCS, Ospedale Policlinico San Martino, 16132 Genoa, Italy
Francesco Lanfranchi
Department of Health Sciences, University of Genoa, 16132 Genoa, Italy
Francesca D’Amico
Department of Health Sciences, University of Genoa, 16132 Genoa, Italy
Silvia Ravera
Department of Experimental Medicine, Human Anatomy, University of Genoa, 16132 Genoa, Italy
Anna Maria Orengo
IRCCS, Ospedale Policlinico San Martino, 16132 Genoa, Italy
Chiara Ghiggi
IRCCS, Ospedale Policlinico San Martino, 16132 Genoa, Italy
Filippo Ballerini
IRCCS, Ospedale Policlinico San Martino, 16132 Genoa, Italy
Paolo Durando
IRCCS, Ospedale Policlinico San Martino, 16132 Genoa, Italy
Sabrina Chiesa
IRCCS, Ospedale Policlinico San Martino, 16132 Genoa, Italy
Alberto Miceli
Department of Health Sciences, University of Genoa, 16132 Genoa, Italy
Maria Isabella Donegani
Department of Health Sciences, University of Genoa, 16132 Genoa, Italy
Silvia Morbelli
IRCCS, Ospedale Policlinico San Martino, 16132 Genoa, Italy
Silvia Bruno
Department of Experimental Medicine, Human Anatomy, University of Genoa, 16132 Genoa, Italy
Gianmario Sambuceti
IRCCS, Ospedale Policlinico San Martino, 16132 Genoa, Italy
Background. The redox stress caused by Hodgkin’s lymphoma (HL) also involves the peripheral blood mononucleated cells (PBMCs) even before chemotherapy. Here, we tested whether lymphocytes and monocytes show a different response to the increased mitochondrial generation of reactive oxygen species (ROS). Methods. PBMCs, isolated from the blood of treatment-naïve HL patients and control subjects, underwent assessment of malondialdehyde content and enzymatic activity of both hexose- and glucose-6P dehydrogenase (H6PD and G6PD) as well as flow cytometric analysis of mitochondrial ROS content. These data were complemented by evaluating the uptake of the fluorescent glucose analogue 2-NBDG that is selectively stored within the endoplasmic reticulum (ER). Results. Malondialdehyde content was increased in the whole population of HL PBMCs. The oxidative damage matched an increased activity of G6PD, and even more of H6PD, that trigger the cytosolic and ER pentose phosphate pathways, respectively. At flow cytometry, the number of recovered viable cells was selectively decreased in HL lymphocytes that also showed a more pronounced increase in mitochondrial ROS generation and 2-NBDG uptake, with respect to monocytes. Conclusions. PBMCs of HL patients display a selective mitochondrial and ER redox stress most evident in lymphocytes already before the exposure to chemotherapy toxicity.