Involment of p53, Bax, and Bcl‐2 pathway in microcystins‐induced apoptosis in rat testis

Abstract

It has been reported that microcystins (MCs) could accumulate in the gonads of mammals and MCs exposure exerts obvious toxic effects on male reproductive system of mammals. We have comfirmed that MCs could accumulate and induce apoptosis in rat testis. The p53, Bax, and Bcl-2 protein play important roles in mitochondria-dependent apoptotic pathway, and this study aimed to investigate whether the p53, Bax, and Bcl-2 pathway is involved in microcystins-induced apoptosis in rat testis and discussed the possible mechanisms. Our results show that MCs led to persistent increase of transcriptional and protein level of P53 and Bax expression but led to decrease of Bcl-2 expression, resulting in an increased ratio of Bax to Bcl-2, which might contribute to apoptotic cell death of rat testis following MCs treatment. The increased ratio of expression of Bax to that of Bcl-2 induced by MCs suggests their important role in MCs-induced apoptosis in rat testis tissue.

A review of reproductive toxicity of microcystins

“…Because Sertoli cells are the main cells expressing FasL in seminiferous tubules and Fas is localized to specific germ cell subtypes, the authors believed that MCs can cause damage directly to Sertoli cells. Li et al [58] also confirmed that MCs could induce apoptosis in testis of Wistar rats that received i.v. injection of CCEs, and p53, Bax, and Bcl-2 might contribute to the mitochondria-dependent apoptotic pathway.…”

“…The competition between Bax and Bcl-2 determines the cell fate in terms of execution of apoptosis or survival. However, MCs induced expression of p53 and the ratio of Bax to Bcl-2 [58], led to the opening of MPT pores, mitochondrial swelling (a common feature of mitochondrial membrane permeabilization) [33], loss of inner mitochondrial membrane potential (MMP), and mitochondrial release of cyt c [123]. Once cyt c is released from the intermembrane space of mitochondria to the cytoplasm, the cell is committed to die by activation of the apoptotic caspase cascade and nucleic DNA fragmentation, or necrosis due to collapse of the respiratory function [72].…”

“…Recently, many studies showed that MCs induced the apoptosis of testicular cells and that the expression of several apoptosis-related proteins was significantly changed, suggesting the important role of apoptosis in MC-induced reproductive toxicity [33,57,58,64,[71][72][73]. An apoptotic DNA ladder was detected in cultured rat Leydig cells by exposure to MC-LR [62].…”

No association ofTP53 codon 72 SNP with male infertility: a study in a Chinese population and a meta-analysis

“…As a tumor suppressor gene, the expression of P53 has been reported to be upregulated in rat testis exposed to microcystins, which showed that the P53 pathway is involved in microcystin-induced apoptosis [Li et al 2011]. Variants of codon 72 of the TP53 gene were described to be associated with the differential expression of the gene in cultured cells [Shi et al 2009].…”

Microcystin-LR stabilizes c-myc protein by inhibiting protein phosphatase 2A in HEK293 cells

“…Total RNA isolation, synthesis of first-strand cDNA, and real-time PCR were performed followed the method described previously (Li et al, 2011). Briefly, HEK293 cells were cultured with 0 or 10 M MC-LR, and the cells were harvested 10 h after treatment.…”