Novel insights into the evolution of the caveolin superfamily and mechanisms of antiapoptotic effects and cell proliferation in lamprey.

Caveolin-1 is the main structural and functional component of caveolin, and it is involved in the regulation of cholesterol transport, endocytosis, and signal transduction. Moreover, changes in caveolin-1 play an important role in tumorigenesis and inflammatory processes. Previous studies have demonstrated that human caveolin-1 is mainly located in the cell membrane and exhibits cell type- and stage-dependent functional differences during cancer development and inflammatory responses. However, the role of Lamprey-caveolin-like (L-caveolin-like) in lamprey remained unknown. Here, we demonstrated that L-caveolin-like performs anti-inflammation and oncogenic functions and the function of caveolin-1 diverged during vertebrate evolution. Moreover, the results reveal the mechanism underlying the antiapoptotic effects of L-caveolin-like. An L-caveolin-like gene from Lampetra japonica (L. japonica) was identified and characterized. L-Caveolin-like was primarily distributed in the leukocytes, intestines and supraneural bodies (Sp-bodies) immune organs as indicated by Q-PCR and immunohistochemistry assays. The mRNA and protein expression levels of L-caveolin exhibited consistent increases in expression at 2 and 72 h in adult tissues after exposure to lipopolysaccharide (LPS) and in leukocytes stimulated by Vibrio anguillarum (V. anguillarum), Staphylococcus aureus (S. aureus), and Poly I:C. Furthermore, the overexpression of pEGFP-N1-L-caveolin-like was associated with a distinct localization in mitochondria, with decreased cytochrome C (Cyt C) and mitochondrial Cyt C oxidase subunit I (CO I) expression. In addition, increased cellular ATP levels suggested that this protein prevented mitochondrial damage. The overexpression of pEGFP-N1-L-caveolin-like led to the altered expression of factors related to apoptosis, such as decreased Caspase-9, Caspase-3, p53, and Bax expression and increased Bcl-2 expression. In addition, the overexpression of pEGFP-N1-L-caveolin-like promoted cell proliferation associated with upregulated EGF, bFGF, and PDGFB expression. Together, these findings indicated that the L-caveolin-like protein from L. japonica induced the activation of antiapoptotic effects via the mitochondrial Cyt C-mediated Caspase-3 signaling pathway. Our analysis further suggests that L-caveolin-like is an oncogene protein product and anti-inflammatory molecule from lamprey that evolved early in vertebrate evolution.