RESUMO
Taking into account homeostatic disorders resulting from arterial hypertension and the key importance of CacyBP/SIP, ß-catenin and endocannabinoids in the functioning of many organs, it was decided to assess the presence and distribution of CacyBP/SIP, ß-catenin, CB1 and CB2 in the adrenal glands of hypertensive rats of various aetiology. The study was conducted on the adrenal glands of rats with spontaneous and renovascular hypertension. The expression of CacyBP/SIP, ß-catenin, CB1 and CB2 was detected by immunohistochemistry and real-time PCR method. The results of the present study revealed both lower gene expression and immunoreactivity of CacyBP/SIP in the adrenal glands of all hypertensive groups compared to the normotensive rats. This study demonstrated a reduction in the immunoreactivity and expression of the ß-catenin, CB1 and CB2 genes in the adrenals of 2K1C rats. While in SHR, the reaction showing ß-catenin and CB1 was very weak or negative, and the expression of CB2 in the adrenal glands of these rats increased. The results of this study show, for the first time, marked differences in the expression of CacyBP/SIP, ß-catenin and CB1 and CB2 cannabinoid receptors in the adrenal glands of rats with primary (SHR) and secondary hypertension (2K1C).
Assuntos
Glândulas Suprarrenais , Hipertensão , Receptor CB1 de Canabinoide , Receptor CB2 de Canabinoide , beta Catenina , Animais , Masculino , Ratos , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , beta Catenina/metabolismo , beta Catenina/genética , Hipertensão/metabolismo , Hipertensão/genética , Hipertensão Renovascular/metabolismo , Hipertensão Renovascular/genética , Hipertensão Renovascular/patologia , Imuno-Histoquímica , Ratos Endogâmicos SHR , Ratos Wistar , Receptor CB1 de Canabinoide/metabolismo , Receptor CB1 de Canabinoide/genética , Receptor CB2 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/genética , Receptores de Canabinoides/metabolismo , Receptores de Canabinoides/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismoRESUMO
The prognosis for patients with RCC is very poor because this cancer is diagnosed mainly in the metastatic stage and is resistant to radio- and chemotherapy. According to recent research, CacyBP/SIP exhibits phosphatase activity against MAPK and may be involved in many cellular processes. This function has not been studied in RCC so far, so we decided to test whether CacyBP/SIP has phosphatase function against ERK1/2 and p38 in high-grade clear cell RCC. The research material consisted of fragments of clear cell RCC, whereas the comparative material consisted of the adjacent normal tissues. Immunohistochemistry and qRT-PCR were used to identify the expression of CacyBP/SIP, ERK1/2, and p38. The studies showed an increase in immunoreactivity and gene expression of the parameters examined in clear cell RCC compared with normal tissues. Only in the case of ERK1/2 was it shown that the expression of the MAPK3 gene was downregulated and the MAPK1 gene was higher in clear cell RCC. These studies demonstrated that CacyBP/SIP lacked phosphatase function against ERK1/2 and p38 in high-grade clear cell RCC. Further research is needed because a better understanding of the role of CacyBP/SIP and MAPK offers hope for the treatment of urological cancer.
Assuntos
Proteínas de Ligação ao Cálcio , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Neoplasias Renais/genética , Sistema de Sinalização das MAP Quinases , Monoéster Fosfórico Hidrolases/metabolismo , FosforilaçãoRESUMO
Hypertension is a global civilization disease and one of the most common causes of death in the world. Organ dysfunction is a serious health consequence of hypertension, which involves damage to the heart, kidneys and adrenals. The interaction of recently discovered multifunctional protein-CacyBP/SIP with ERK1/2 and p38 kinases by regulating the activity and intracellular localization of these kinases may play an important role in the signaling pathways involved in the pathogenesis of hypertension. Due to the lack of data on this subject, we decided to investigate the localization, expression and possible relationship between the studied parameters in the adrenals under arterial hypertension. The study was conducted on the adrenals of rats with spontaneous and DOCA-salt hypertension. The expression of CacyBP/SIP, p-ERK1/2 and p-p38 was detected by immunohistochemistry and qRT-PCR. The results show a statistically significant decrease in CacyBP/SIP expression in the adrenal glands of hypertensive rats. With ERK1/2, there was a decrease in cortical immunoreactivity and an increase in the adrenal medulla of primary hypertensive rats. In contrast, in the adrenals of DOCA-salt rats, ERK1/2 immunoreactivity increased in the cortex and decreased in the medulla. In turn, p38 expression was higher in the adrenal glands of rats with primary and secondary hypertension. The obtained results may suggest the involvement of CacyBP/SIP in the regulation of signaling pathways in which MAP kinases play an important role and provide new insight into molecular events in hypertension. Moreover, they show the participation of CacyBP/SIP in response to oxidative stress.