RESUMO
Nuclear receptors were originally defined as endocrine sensors in humans, leading to the identification of the nuclear receptor superfamily. Despite intensive efforts, most nuclear receptors have no known ligand, suggesting new ligand classes remain to be discovered. Furthermore, nuclear receptors are encoded in the genomes of primitive organisms that lack endocrine signaling, suggesting the primordial function may have been environmental sensing. Here we describe a novel Caenorhabditis elegans nuclear receptor, HIZR-1, that is a high zinc sensor in an animal and the master regulator of high zinc homeostasis. The essential micronutrient zinc acts as a HIZR-1 ligand, and activated HIZR-1 increases transcription of genes that promote zinc efflux and storage. The results identify zinc as the first inorganic molecule to function as a physiological ligand for a nuclear receptor and direct environmental sensing as a novel function of nuclear receptors.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Homeostase/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/metabolismo , Zinco/farmacologia , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Proteínas de Transporte de Cátions/genética , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , DNA/metabolismo , Elementos Facilitadores Genéticos/genética , Retroalimentação Fisiológica/efeitos dos fármacos , Testes Genéticos , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Ligantes , Mutação/genética , Regiões Promotoras Genéticas/genética , Domínios Proteicos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Citoplasmáticos e Nucleares/química , Receptores Citoplasmáticos e Nucleares/genética , Transcrição Gênica/efeitos dos fármacosRESUMO
BACKGROUND: Paget-Schroetter syndrome (PSS) is a rare condition of axillosubclavian vein thrombosis often seen in athletes with a history of repetitive external rotation and abduction of the shoulder. The purpose of this review was to analyze the literature and characterize PSS in the athletic population, including risk of PSS by sport. We also provide a comprehensive review of PSS to inform clinicians on the pathophysiology, detection, and management of the condition. METHODS: Four databases were reviewed to identify cases of PSS occurring in athletes. Data on patient demographics, reported sport, diagnosis, treatment, management, return to sport, and complications were extracted and analyzed by 2 independent reviewers. RESULTS: Of the 123 cases of PSS identified, baseball and weight lifting had the highest incidence (26.8% and 19%, respectively), followed by swimming, football, and basketball. The average return to sport was 4.7 months, and 26.7% of subjects reported complications, most commonly pulmonary embolism. CONCLUSION: In athletes presenting with upper extremity pain and swelling with a history of playing baseball or weight lifting, PSS should be higher on a clinicians differential diagnosis list. Swimmers, football, and basketball players are less likely to present with PSS but are still more likely than other types of athletes to develop the condition. Clinician awareness of PSS in athletes is critical to avoid delays in treatment and misdiagnosis, and to allow for a timely return to sport with minimal complications.