Disease relevance of Bnip3l

• Thus, Nix/Bnip3L is upregulated in myocardial hypertrophy, and is both necessary and sufficient for Gq-mediated apoptosis of cardiomyocytes and resulting hypertrophy decompensation [1].
• Mitochondrial death protein Nix is induced in cardiac hypertrophy and triggers apoptotic cardiomyopathy [1].
• In contrast, Nix transcription was increased by phenylephrine but not by isoproterenol, angiotensin II, or hypoxia [2].
• In vivo determinants of Nix expression were evaluated in Nix promoter-luciferase (NixP) transgenic mice that underwent ischemia-reperfusion (1 h/24 h), transverse aortic coarctation (TAC), or cross-breeding with the G(q) overexpression model of hypertrophy [2].
• Unlike normal postnatal cardiac growth, concurrent left ventricular pressure overload hypertrophy did not synergize with Nix expression to cause cardiomyopathy or myocardial apoptosis [3].

High impact information on Bnip3l

• A previously undescribed truncated Nix isoform, termed sNix, was not targeted to mitochondria but heterodimerized with Nix and protected against Nix-mediated apoptosis [1].
• To identify mechanisms of gene regulation for these critical cardiac apoptosis effectors, the determinants of Nix and BNip3 promoter activation were elucidated by luciferase reporter gene expression in neonatal rat cardiac myocytes [2].
• NixP activity was proportional to the extent of TAC hypertrophy and was inhibited by mithramycin [2].
• Human Nip3 maps to chromosome 14q11.2-q12, whereas Nix/BNip3L was found on 8q21 [4].
• Following transfection, Nix protein undergoes progressive proteolysis to an 11-kDa C-terminal fragment, which is blocked by the proteasome inhibitor lactacystin [4].

Biological context of Bnip3l

• Up-regulation of myocardial Nix and BNip3 is associated with apoptosis in cardiac hypertrophy and ischemia, respectively [2].

References