Thyroid hormone in the frontier of cell protection, survival and functional recovery

Abstract

Thyroid hormone (TH) exerts important actions on cellular energy metabolism, accelerating O2 consumption with consequent reactive oxygen species (ROS) generation and redox signalling affording cell protection, a response that is contributed by redox-independent mechanisms. These processes underlie genomic and non-genomic pathways, which are integrated and exhibit hierarchical organisation. ROS production led to the activation of the redox-sensitive transcription factors nuclear factor-κB, signal transducer and activator of transcription 3, activating protein 1 and nuclear factor erythroid 2-related factor 2, promoting cell protection and survival by TH. These features involve enhancement in the homeostatic potential including antioxidant, antiapoptotic, antiinflammatory and cell proliferation responses, besides higher detoxification capabilities and energy supply through AMP-activated protein kinase upregulation. The above aspects constitute the molecular basis for TH-induced preconditioning of the liver that exerts protection against ischemia-reperfusion injury, a strategy also observed in extrahepatic organs of experimental animals and with other types of injury, which awaits application in the clinical setting. Noteworthy, re-adjusting TH to normal levels results in several beneficial effects; for example, it lengthens the cold storage time of organs for transplantation from brain-dead donors; allows a superior neurological outcome in infants of <28 weeks of gestation; reduces the cognitive side-effects of lithium and improves electroconvulsive therapy in patients with bipolar disorders.

The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications

“…In humans, an adequate supply of I − at the very beginning of life is critical for preventing I − deficiency disorders (IDDs) that can lead to severe and irreversible cognitive and physical impairments (13, 14). THs are required for the development and maturation of the central nervous system, lungs, and skeletal muscle (15) and are also key regulators of metabolism in all cells (16). Women of reproductive age are one of the demographic groups most susceptible to IDDs because I − deficiency is directly related to reproductive failure and is associated with perinatal mortality (17, 18).…”

Redox signaling associated with thyroid hormone action: perspectives in medical sciences

“…Nongenomic mechanisms of TH action are triggered without the participation of nTRs, involve cell surface receptors, extranuclear TR β , or TR α derivatives, which trigger complex nuclear and cellular effects [2]. These include cell proliferation [7], angiogenesis [8], intracellular protein trafficking [2], activation of enzymes such as mitochondrial cytochrome-c oxidase [9] and plasma membrane Na + K + -ATPase [10], and the activation of transcription factors and enzymes by low levels of reactive oxygen species (ROS) [11], leading to redox-modulated cell signaling [12,13].…”

Anti-apoptotic effects of 3,3’,5-triiodo-l-thyronine in the liver of brain-dead rats

“…However, there remains controversy about the effectiveness of thyroid therapy due to varying degrees of success. Moreover, the mechanisms behind the therapeutic effects of thyroid hormones are only beginning to be understood [22]. Even though reports have shown beneficial effects of thyroid hormone replacement on the hemodynamic status of the donor, no conclusive evidence has been published [23][24][25][26].…”