Expression ofbcl-2family of genes during resection induced liver regeneration: Comparison between hepatectomized and sham groups

Abstract

AIM: During liver regeneration cellular proliferation and apoptosis result in tissue remodeling to restore normal hepatic mass and structure. Main regulators of the apoptotic machinery are the Bcl-2 family proteins but their roles are not well defined throughout the liver regeneration. We aimed to analyze the expression levels of bcl-2 gene family members during resection induced liver regeneration. METHODS:We performed semi-quantitative RT-PCR to examine the expression level of bak, bax, bcl-2 and bcl-x L in the 70% hepatectomized rat livers during the whole regeneration process and compared to that of the sham and normal groups. RESULTS:The expression of bak and bax were decreased whereas bcl-2 and bcl-x L were increased in hepatectomized animals compared to normal liver at most time points. We also reported for the first time that sham group of animals had statistically significant higher expression of bak and bax compared to hepatectomized animals. In addition, the area under the curve (AUC) values of these genes were more in sham groups than the hepatectomized groups. CONCLUSION:We conclude that the expressional changes of bak, bax, bcl-2 and bcl-x L genes were altered not only due to regeneration, but also due to the effects of surgical operations.Akcali KC, Dalgic A, Ucar A, Ben Haj K, Guvenc D. Expression of bcl-2 family of genes during resection induced liver regeneration: Comparison between hepatectomized and sham groups. World

Roles of Fas/Fasl, Bcl-2/Bax, and Caspase-8 in rat nonalcoholic fatty liver disease pathogenesis

“…In the NAFLD formation process, fat degeneration and oxidative stress could increase Bax synthesis and move outside of the mitochondrial membrane, thereby changing the configuration and forming homodimers, inducing the opening of the mitochondrial PT pore and the release of cytochrome C, which would further induce apoptosis. Bcl-2 is mainly distributed in the outer mitochondrial membrane; its homodimer would suppress the opening of the PT pore, and its combination with Bax could prevent Bax's conformational change and thus play a role in antiapoptosis (Pastorino et al, 2003;Akcali et al, 2004). Therefore, Bcl-2 inhibits apoptosis while Bax promotes apoptosis, and the ratio of the Bcl-2/Bax protein complex is directly related to the occurrence of apoptosis.…”

Modelos de regeneração hepática em animais em crescimento: estudos histológicos, moleculares e avaliação de efeitos de imunossupressores

“…[21][22][23][24] Devido à relevância dos fenômenos regenerativos no fígado transplantado e a possibilidade de interferência de múltiplos fatores, quer endógenos quer exógenos, desperta-se o interesse pela possível ação das drogas imunossupressoras sobre a regeneração hepática, pois tais drogas constituem a base do tratamento após o transplante de órgãos sólidos.…”

“…O envolvimento desses genes foi descrito em modelos de regeneração em animais adultos. [21][22][23][24] No presente trabalho investigou-se a expressão de genes relacionados à apoptose no parênquima dos animais submetidos à hepatectomia parcial e à cirurgia simulada, a fim de verificar também os efeitos do trauma cirúrgico isolado.…”

“…Nos animais recém-desmamados a expressão do Bcl-2 aumentou significativamente após a hepatectomia (Gráfico 5). Tais resultados são similares aos obtidos com estudos em ratos adultos 23,24 e sugerem que a relação entre a expressão dos genes pró e anti-apoptóticos favoreceu os fenômenos proliferativos das células durante a regeneração, com inibição da morte celular programada.…”

“…75 Em cultura de hepatócitos de ratos, a ciclosporina teve uma ação dose-dependente, com ativação de caspases pelo citocromo c e aumento do número de células TUNEL positivas. No fígado, a proteína Bcl-2 não é produzida nos hepatócitos, e sim nas células não-parenquimatosas, principalmente colangiocitos 21,23 . Desta forma, o aumento da expressão desse gene não se refletiu como diminuição na quantidade de hepatócitos em apoptose.…”