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Study · Ex vivo tissue · 2005

8 results

Humanin binds and nullifies Bid activity by blocking its activation of Bax and Bak.

Zhai D, Luciano F, Zhu X, Guo B, Satterthwait AC, Reed JC

The Journal of biological chemistry20 Jan 2005Cited by 120 (Europe PMC)

PMID15661737 (opens in a new tab)DOI10.1074/jbc.m411902200 (opens in a new tab)PepBankPUB-15661737
Publisher pagePubMedAsk about this study
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Summary

Recently, we discovered that Humanin (HN), a small endogenous peptide of 24 amino acids, binds to and inhibits the proapoptotic protein Bax. We show here that HN also interacts with the BH3-only Bcl-2/Bax family protein, Bid, as well as a truncated form of Bid (tBid) associated with protease-mediated activation of this proapoptotic protein. Synthetic HN peptide binds purified Bid and tBid in vitro and blocks tBid-induced release of cytochrome c and SMAC from isolated mitochondria, whereas mutant peptides that fail to bind Bid or tBid lack this activity. Moreover, HN peptide also retained protective activity on bax-/-mitochondria, indicating that HN can block tBid-induced release of apoptogenic proteins from these organelles in a Bax-independent manner. HN peptide inhibits tBid-induced oligomerization of Bax and Bak in mitochondrial membranes, as shown by experiments with chemical cross-linkers or gel filtration. Gene transfection experiments showed that HN (but not an inactive mutant of HN) also protects intact cells from apoptosis induced by overexpression of tBid. We conclude that Bid represents an additional cellular target of HN, and we propose that HN-mediated suppression of Bid contributes to the antiapoptotic activity of this endogenous peptide.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

6 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabEx vivo tissueMechanism

    In isolated mitochondria, synthetic humanin blocked tBid-induced release of cytochrome c.

    In plain wordsIn lab tests on isolated mitochondria, synthetic humanin blocked the release of cytochrome c caused by tBid.

    Peptide
    Humanin
    Outcome
    DecreasetBid-induced cytochrome c release from mitochondria
    Study

    n: not reported in source

    isolated mitochondria
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    blocks tBid-induced release of cytochrome c and SMAC from isolated mitochondria
  2. 02LabEx vivo tissueMechanism

    In isolated mitochondria, synthetic humanin blocked tBid-induced release of SMAC.

    In plain wordsIn lab tests on isolated mitochondria, synthetic humanin blocked the release of SMAC caused by tBid.

    Peptide
    Humanin
    Outcome
    DecreasetBid-induced SMAC release from mitochondria
    Study

    n: not reported in source

    isolated mitochondria
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    blocks tBid-induced release of cytochrome c and SMAC from isolated mitochondria
  3. 03LabEx vivo tissueMechanism

    Humanin peptide retained protective activity on bax-/- mitochondria, so it blocked tBid-induced release of apoptogenic proteins independently of Bax.

    In plain wordsIn lab tests on isolated mitochondria without Bax, humanin still blocked the release of cell-death proteins caused by tBid.

    Peptide
    Humanin
    Outcome
    DecreaseProtection of bax-/- mitochondria from tBid
    Study

    n: not reported in source

    bax-/- mitochondria
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Moreover, HN peptide also retained protective activity on bax-/-mitochondria, indicating that HN can block tBid-induced release of apoptogenic proteins from these organelles in a Bax-independent manner.
  4. 04LabEx vivo tissueMechanism

    In mitochondrial membranes, humanin peptide inhibited tBid-induced oligomerization of Bax.

    In plain wordsIn lab tests on mitochondrial membranes, humanin stopped tBid from causing Bax proteins to clump together.

    Peptide
    Humanin
    Outcome
    DecreasetBid-induced Bax oligomerization
    Study

    n: not reported in source

    mitochondrial membranes
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    HN peptide inhibits tBid-induced oligomerization of Bax and Bak in mitochondrial membranes, as shown by experiments with chemical cross-linkers or gel filtration.
  5. 05LabEx vivo tissueMechanism

    In mitochondrial membranes, humanin peptide inhibited tBid-induced oligomerization of Bak.

    In plain wordsIn lab tests on mitochondrial membranes, humanin stopped tBid from causing Bak proteins to clump together.

    Peptide
    Humanin
    Outcome
    DecreasetBid-induced Bak oligomerization
    Study

    n: not reported in source

    mitochondrial membranes
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    HN peptide inhibits tBid-induced oligomerization of Bax and Bak in mitochondrial membranes, as shown by experiments with chemical cross-linkers or gel filtration.
  6. 06LabIn vitro (cell-free)Mechanism

    In vitro, synthetic humanin peptide bound purified Bid and tBid.

    In plain wordsIn lab tests, synthetic humanin attached to the cell-death proteins Bid and tBid.

    Peptide
    Humanin
    Outcome
    Not applicableHN binding to Bid and tBid
    Study

    n: not reported in source

    purified Bid and tBid in vitro
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Synthetic HN peptide binds purified Bid and tBid in vitro

Studies that did not test the peptide alone2

In this study, Humanin was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Humanin.

  1. 07LabNot a test of Humanin aloneEx vivo tissueMechanism

    Mutant humanin peptides that failed to bind Bid or tBid lacked the ability to block tBid-induced release of cytochrome c and SMAC.

    In plain wordsIn lab tests, changed humanin peptides that could not bind Bid or tBid did not block the release of cell-death signals.

    Peptide
    Humanin
    Outcome
    No significant changeActivity of mutant HN peptides that fail to bind Bid or tBid
    Study

    n: not reported in source

    isolated mitochondria
    Outcome group
    Receptor activity and mechanism · Pharmacology

    Source sentences

    Summary
    whereas mutant peptides that fail to bind Bid or tBid lack this activity.

    In this study, Humanin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Humanin.

  2. 08LabNot a test of Humanin aloneIn vitro (cells)Mechanism

    In gene transfection experiments, humanin, but not an inactive mutant, protected intact cells from apoptosis induced by tBid overexpression.

    In plain wordsIn cells where genes were transferred, humanin but not an inactive changed version protected against cell death caused by tBid.

    Peptide
    Humanin
    Outcome
    DecreaseProtection of intact cells from tBid-induced apoptosis (gene transfection)
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Pharmacology

    Source sentences

    Summary
    Gene transfection experiments showed that HN (but not an inactive mutant of HN) also protects intact cells from apoptosis induced by overexpression of tBid.

    In this study, Humanin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Humanin.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    13 Oct 2026, 21:44 UTC

    Study results updated

  2. Version 1

    13 Oct 2026, 16:31 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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