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1.
Am J Physiol Gastrointest Liver Physiol ; 319(6): G733-G747, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33052704

RESUMO

Selective autophagy of the endoplasmic reticulum (ER), namely ER-phagy, is mediated by ER-localized receptors, which are recognized and sequestered by GABARAP/LC3B-decorated phagophores and transferred to lysosomes for degradation. Being one such receptor, FAM134B plays critical roles in cellular processes such as protein quality control and neuronal survival. FAM134B has also been associated with different cancers, although its exact role remains elusive. We report here that the FAM134B gene encodes not one but at least two different protein isoforms: the full-length and the NH2 terminally truncated forms. Their relative expression shows extreme variation, both within normal tissues and among cancer types. Expression of full-length FAM134B is restricted to the brain, testis, spleen, and prostate. In contrast, NH2 terminally truncated FAM134B is dominant in the heart, skeletal muscle, kidney, pancreas, and liver. We compared wild-type and knockout mice to study the role of the Fam134b gene in starvation. NH2 terminally truncated FAM134B-2 was induced in the liver, skeletal muscle, and heart but not in the pancreas and stomach following starvation. Upon starvation, Fam134b-/- mice differed from wild-type mice by less weight loss and less hyperaminoacidemic and hypocalcemic response but increased levels of serum albumin, total serum proteins, and α-amylase. Interestingly, either NH2 terminally truncated FAM134B or both isoforms were downregulated in liver, lung, and colon cancers. In contrast, upregulation was observed in stomach and chromophobe kidney cancers.NEW & NOTEWORTHY We reported tissues expressing FAM134B-2 such as the kidney, muscle, heart, and pancreas, some of which exhibit stimulated expression upon nutrient starvation. We also demonstrated the effect of Fam134b deletion during ad libitum and starvation conditions. Resistance to weight loss and hypocalcemia, accompanied by an increase in serum albumin and α-amylase levels, indicate critical roles of Fam134b in physiology. Furthermore, the differential expression of FAM134B isoforms was shown to be significantly dysregulated in human cancers.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Neoplasias/genética , Neoplasias/metabolismo , Adulto , Animais , Autofagia , Linhagem Celular Tumoral , Retículo Endoplasmático/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Isomerismo , Masculino , Camundongos , Camundongos Knockout , Inanição/metabolismo , Distribuição Tecidual
2.
Vet Res Forum ; 13(3): 293-299, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36320297

RESUMO

Toxoplasma gondii is a protozoon parasite which causes toxoplasmosis both in human and warm-blooded animals. Toxoplasmosis is a worldwide disease and largely threats human and animal health consequently causing economic losses. Also, it affects the visceral organs in different severity degrees according to the strain of parasite and the host. In this study, experimental toxoplasmosis was performed via intra-peritoneal route in 12 gerbils by administrating 5.00 × 103 tachyzoites of T. gondii RH strain. The gerbils were sacrificed 7 days after inoculation. All systemic organs were obtained via necropsy and examined by immunohistochemical and histopathological methods. Lesions infected with T. gondii mostly observed in the serosa of abdominal cavity organs including stomach, liver, spleen, intestines, and kidneys. The lesions were most severe in liver. The parasite showed an affinity for the hepatic tissue. To our knowledge, this is the first experimental study of acute T. gondii infection in gerbil evaluating macroscopic, microscopic and immunohistochemical findings. It is concluded that Mongolian gerbils can be used as experimental animals to investigate toxoplasmosis. Also, these animals are very suitable hosts to study liver pathology and pathobiology of T. gondii-related hepatitis.

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