Tumor suppressor p53 induces apoptosis of host lymphocytes experimentally infected by Leishmania major, by activation of Bax and caspase-3: a possible survival mechanism for the parasite.

Abstract

Apoptosis of infected host macrophages by Leishmania spp. is mainly addressed as one of the survival mechanisms of the parasite. However, there is no eligible data about whether tumor suppressor p53 could induce the apoptosis of host lymphocytes-treated Leishmania major via the mitochondrial intrinsic pathway. In this study, the amastigotes of L. major obtained from ten cutaneous leishmaniases (CL) patients were separately isolated and cultured in N.N.N and RPMI 1640 media. L. major was definitely confirmed by targeting Cyt b gene following sequencing. Subsequently, 2-3 × 106 lymphocytes obtained from ten healthy individuals were isolated and co-cultured with 1-2 × 106 L. major promastigotes. Following 6 h of exposure time, the enzymatic activity of caspase-3 was determined by fluorometric assay in each L. major-treated lymphocytes and cell control (only lymphocyte). The mRNA expressions of Bax, Bcl-2, p53, and caspase-3 genes were assessed by quantitative real-time-PCR analysis following 6 to 9 h of exposure times. The Bcl-2 mRNA expression in L. major-treated lymphocytes was 100-fold down-regulated relative to cell control. The mRNA expressions of p53 and caspase-3 were over-expressed 1.8- and 3.2-fold up-regulated relative to control lymphocytes, respectively. The Bax/Bcl-2 ratio and caspase-3 activity were higher than the control group (Pv <0.05). The current new findings indicate that the apoptotic effects of L. major-treated host lymphocytes dependent on p53 tumor suppressor via mitochondrial pathway may probably address as an auxiliary survival mechanism of L. major in CL patients. However, here is much work ahead to figure out the multiple functions played by apoptosis in the evasion of L. major.

• Authors: Mozhgan Moshrefi, Adel Spotin, Hossein Samadi Kafil, Mahmoud Mahami-Oskouei, Behzad Baradaran, Ehsan Ahmadpour, Behzad Mansoori
• Journal: Parasitology research (Parasitol Res) Vol. 116 Issue 8 Pg. 2159-2166 (Aug 2017) ISSN: 1432-1955 [Electronic] Germany
• PMID: 28560572 (Publication Type: Journal Article)

Chemical References

• Proto-Oncogene Proteins c-bcl-2
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• Caspase 3

Topics

• Adolescent
• Adult
• Animals
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Child
• Enzyme Activation
• Female
• Humans
• Leishmania major (physiology)
• Leishmaniasis, Cutaneous (enzymology, parasitology)
• Lymphocytes (parasitology)
• Male
• Mitochondria (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (genetics)
• Tumor Suppressor Protein p53 (metabolism)
• Young Adult
• bcl-2-Associated X Protein (genetics, metabolism)