DJ-1 Deficiency Protects against Sepsis-Induced Myocardial Depression
James N. Tsoporis,
Hajera Amatullah,
Sahil Gupta,
Shehla Izhar,
Amin M. Ektesabi,
Chirag M. Vaswani,
Jean-Francois Desjardins,
Golam Kabir,
Ana Paula Teixera Monteiro,
Amir K. Varkouhi,
Nikolaos Kavantzas,
Vasileios Salpeas,
Ioannis Rizos,
John C. Marshall,
Thomas G. Parker,
Howard Leong-Poi,
Claudia C. dos Santos
Affiliations
James N. Tsoporis
The Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada
Hajera Amatullah
The Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada
Sahil Gupta
The Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada
Shehla Izhar
The Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada
Amin M. Ektesabi
The Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada
Chirag M. Vaswani
The Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada
Jean-Francois Desjardins
The Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada
Golam Kabir
The Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada
Ana Paula Teixera Monteiro
The Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada
Amir K. Varkouhi
The Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada
Nikolaos Kavantzas
1st Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
Vasileios Salpeas
1st Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
Ioannis Rizos
2nd Department of Cardiology, Attikon University Hospital, 12462 Athens, Greece
John C. Marshall
The Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada
Thomas G. Parker
The Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada
Howard Leong-Poi
The Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada
Claudia C. dos Santos
The Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada
Oxidative stress is considered one of the early underlying contributors of sepsis-induced myocardial depression. DJ-1, also known as PARK7, has a well-established role as an antioxidant. We have previously shown, in a clinically relevant model of polymicrobial sepsis, DJ-1 deficiency improved survival and bacterial clearance by decreasing ROS production. In the present study, we investigated the role of DJ-1 in sepsis-induced myocardial depression. Here we compared wildtype (WT) with DJ-1 deficient mice at 24 and 48 h after cecal ligation and puncture (CLP). In WT mice, DJ-1 was increased in the myocardium post-CLP. DJ-1 deficient mice, despite enhanced inflammatory and oxidative responses, had an attenuated hypertrophic phenotype, less apoptosis, improved mitochondrial function, and autophagy, that was associated with preservation of myocardial function and improved survival compared to WT mice post-CLP. Collectively, these results identify DJ-1 as a regulator of myocardial function and as such, makes it an attractive therapeutic target in the treatment of early sepsis-induced myocardial depression.
