Disease relevance of Bid

• The volume of brain infarct is greatly reduced in Bid-deficient mice, thus indicating activation of the mitochondrial pathway by cell-death receptors following focal ischemia [1].
• In contrast, loss of Bid, another BH3-only protein, provided no protection from neonatal HI brain injury [2].
• Sustained phosphorylation of Bid is a marker for resistance to Fas-induced apoptosis during chronic liver diseases [3].
• In controls, activation of the Fas receptor resulted in rapid dephosphorylation of Bid and its subsequent cleavage, whereas Bid remained phosphorylated and uncleaved in chronic cholestasis and other models of hepatic apoptosis resistance [3].
• Oxygen deprivation of human colon cancer cells in vitro provoked decreased mRNA and protein levels of proapoptotic Bid and Bad [4].

High impact information on Bid

• These results establish a link between proapoptotic Bid and the DNA-damage response [5].
• In the absence of Bid, mice accumulate chromosomal aberrations and develop a fatal myeloproliferative disorder resembling chronic myelomonocytic leukemia [5].
• Peptide mass fingerprinting identified this protein as Bid, a BH3 domain-containing protein known to interact with both Bcl2 and Bax [6].
• About half of the Bid-deficient animals had no apparent liver injury and showed no evidence of activation of the effector caspases 3 and 7, although the initiator caspase 8 had been activated [7].
• In these Bid-/- cells, mitochondrial dysfunction was delayed, cytochrome c was not released, effector caspase activity was reduced and the cleavage of apoptosis substrates was altered [7].

Chemical compound and disease context of Bid

• The same ischemic insult induced acute renal failure in Bid-deficient mice, which was nonetheless less severe than the wild-type, showing 1.3 mg/dl serum creatinine [8].
• Mice lacking Bid exhibited significantly less pulmonary fibrosis in response to bleomycin compared with WT mice [9].

Biological context of Bid

• Nonredundant role of Bax and Bak in Bid-mediated apoptosis [10].
• Disruption of the Bid pathway by gene deletion protected against cell death in vivo and in vitro [11].
• We have now examined the role of Bid in anoikis [12].
• Knock down of caspase-2 by short interfering RNA further excluded its role in Bid activation by DNA damage [13].
• CONCLUSIONS: We propose a model in which the phosphorylation status of Bid determines the apoptotic threshold of hepatocytes in vivo [3].

Anatomical context of Bid

• In addition, mitochondria depolarization also could be induced by caspases, whose activation was mainly dependent on Bid [14].
• RESULTS: Studies in wild-type and Bid knockout hepatocytes showed that tumor necrosis factor alpha-mediated lysosomal permeabilization is Bid dependent [15].
• As the differentiation proceeds, the neurons express higher levels of Bid than the stem cells of the paraventricular zone [16].
• Both in embryonic and postnatal life, Bid protein is present in the most vital regions of brain, such as the limbic system, basal ganglia, mesencephalic tectum, Purkinje cells in cerebellum, and the ventral columns of spinal cord [16].
• However, its subsequent insertion into the mitochondrial membrane depends on Bid [17].

Associations of Bid with chemical compounds

• We conclude that Bid, cleaved by an undefined aspartate-specific protease, can be a key mediator of the apoptotic response to DNA-damaging anticancer regimens [13].
• We showed increased activation of both Bid and Bax in A549 cells subjected to hyperoxia [11].
• After treating mice with lipopolysaccharide or TNFalpha in the presence of d-galactosamine, Bid was cleaved and translocated to mitochondria in hepatocytes [17].
• Caspase-8 and Bid were cleaved in Colo357 cells exposed to gemcitabine, and there was no correlation with either Bcl-xL or with Bax expression [18].
• Furthermore, disrupting the function of Hsp90 by the addition of its specific inhibitor, geldanamycin, blocked Hsp90's protection of Bid cleavage [19].

Physical interactions of Bid

• Furthermore, it does not require Bid to interact directly with other Bcl-2 family proteins, such as Bax [12].
• In vitro assays, using purified mitochondria and recombinant proteins, demonstrate that Bfl-1 binds full-length Bid, but does not interfere with its processing by caspase-8, or with its mitochondrial association [20].

Enzymatic interactions of Bid

• In addition, caspase-8 cleaves Bid, the truncated form of which has the capacity to translocate to the mitochondria and induce cytochrome c release [1].
• Moreover, in the absence of the putative transmembrane C-terminal domain, Bax does not form ionic channels in the presence of cut Bid [21].

Regulatory relationships of Bid

• We discovered that Bid--a pro-death Bcl-2 family protein activated by ligated death receptors--was the main intracellular molecule signaling the generation of the radicals by targeting to the mitochondria and that the majority of oxygen radical production was dependent on Bid [22].
• Among proapoptotic proteins, Bax expression was activated in H(2)S-treated cells but not Bid, and the antiapoptotic proteins Bcl-X(L) and Bcl-2 did not show any activation in pancreatic acinar cell apoptosis [23].
• Furthermore, caspase-8 was activated and Bid cleaved [24].
• The expression of Bcl-X(L) protected MLEC against H/R-induced cell death by blocking Bax and Bid translocation and inhibiting mitochondrial cytochrome c release [25].
• Heat shock protein 90 suppresses tumor necrosis factor alpha induced apoptosis by preventing the cleavage of Bid in NIH3T3 fibroblasts [19].

Other interactions of Bid

• The pro-death Bcl-2 family protein, Bid, mediates this pathway by inducing mitochondrial releases of cytochrome c and other apoptotic factors [14].
• Among the Bcl-2 family proteins only Bid and Bcl-XL continue to be expressed at high levels in the adult brain [16].
• We have, for the first time, identified a predominant role for the caspase-8/Bid pathway in signaling associated with hyperoxic lung injury and cell death in vivo and in vitro [11].
• The expression of the pro-apoptotic members Bax, Bak, Bid, and Bcl-x(S) was significantly ( P < 0.05) decreased after TPN [26].
• TNFR1/Fas engagement results in the cleavage of cytosolic Bid to truncated Bid (tBid), which translocates to mitochondria [27].

Analytical, diagnostic and therapeutic context of Bid

• We employed an in vitro reconstitution system as well as cell cultures and an animal model to reflect the physiological environment where Bid could be functional [28].
• In addition, activation of Bid in the wild-type brains could be readily detected at approximately 3 h after ischemia, as evidenced by its proteolytic cleavage and translocation to the mitochondria as determined using Western blot analysis and immunofluorescence staining [29].
• In addition, Bid deficiency attenuated tubular disruption, tubular cell apoptosis, and caspase-3 activation during 48 h of reperfusion [8].
• Treatment of lpr mice with Bid antisense also ameliorated liver injury following bile duct ligation of the mice, a model of extrahepatic cholestasis [30].
• Bands of Bid cleavage and Bax conformational change were detected by Western blot [31].

References