Apoptosis of Hepatocytes: Relevance for HIV-Infected Patients under Treatment
Por:
Gruevska A, Moragrega ÁB, Cossarizza A, Esplugues JV, Blas-García A and Apostolova N
Publicada:
1 feb 2021
Ahead of Print:
16 feb 2021
Categoría:
Biochemistry, genetics and molecular biology (miscellaneous)
Resumen:
Due to medical advances over the past few decades, human immunodeficiency virus (HIV) infection, once a devastatingly mortal pandemic, has become a manageable chronic condition. However, available antiretroviral treatments (cART) cannot fully restore immune health and, consequently, a number of inflammation-associated and/or immunodeficiency complications have manifested themselves in treated HIV-infected patients. Among these chronic, non-AIDS (acquired immune deficiency syndrome)-related conditions, liver disease is one of the deadliest, proving to be fatal for 15-17% of these individuals. Aside from the presence of liver-related comorbidities, including metabolic disturbances and co-infections, HIV itself and the adverse effects of cART are the main factors that contribute to hepatic cell injury, inflammation, and fibrosis. Among the molecular mechanisms that are activated in the liver during HIV infection, apoptotic cell death of hepatocytes stands out as a key pathogenic player. In this review, we will discuss the evidence and potential mechanisms involved in the apoptosis of hepatocytes induced by HIV, HIV-encoded proteins, or cART. Some antiretroviral drugs, especially the older generation, can induce apoptosis of hepatic cells, which occurs through a variety of mechanisms, such as mitochondrial dysfunction, increased production of reactive oxygen species (ROS), and induction of endoplasmic reticulum (ER) stress and unfolded protein response (UPR), all of which ultimately lead to caspase activation and cell death.
Filiaciones:
:
Department of Pharmacology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
FISABIO-Hospital Universitario Dr. Peset, 46017 Valencia, Spain
:
Department of Pharmacology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
FISABIO-Hospital Universitario Dr. Peset, 46017 Valencia, Spain
Cossarizza A:
Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, 41124 Modena, Italy
National Institute for Cardiovascular Research, 40126 Bologna, Italy
:
Department of Pharmacology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
FISABIO-Hospital Universitario Dr. Peset, 46017 Valencia, Spain
National Network of Biomedical Research on Hepatic and Digestive Diseases (CIBERehd), 46010 Valencia, Spain
:
FISABIO-Hospital Universitario Dr. Peset, 46017 Valencia, Spain
National Network of Biomedical Research on Hepatic and Digestive Diseases (CIBERehd), 46010 Valencia, Spain
Department of Physiology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
:
Department of Pharmacology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
FISABIO-Hospital Universitario Dr. Peset, 46017 Valencia, Spain
National Network of Biomedical Research on Hepatic and Digestive Diseases (CIBERehd), 46010 Valencia, Spain
gold, Green Published
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