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1.
Cell Mol Life Sci ; 78(5): 2145-2155, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32844279

RESUMO

BIM is a key apoptotic protein, participating in diverse cellular processes. Interestingly, recent studies have hypothesized that BIM is associated with the extensive neuronal cell death encountered in protein misfolding diseases, such as Alzheimer's disease. Here, we report that the core pro-apoptotic domain of BIM, the BIM-BH3 motif, forms ubiquitous amyloid fibrils. The BIM-BH3 fibrils exhibit cytotoxicity, disrupt mitochondrial functions, and modulate the structures and dynamics of mitochondrial membrane mimics. Interestingly, a slightly longer peptide in which BIM-BH3 was flanked by four additional residues, widely employed as a model of the pro-apoptotic core domain of BIM, did not form fibrils, nor exhibited cell disruptive properties. The experimental data suggest a new mechanistic role for the BIM-BH3 domain, and demonstrate, for the first time, that an apoptotic peptide forms toxic amyloid fibrils.


Assuntos
Amiloide/química , Apoptose , Proteína 11 Semelhante a Bcl-2/química , Domínios Proteicos , Sequência de Aminoácidos , Amiloide/metabolismo , Amiloide/ultraestrutura , Proteína 11 Semelhante a Bcl-2/genética , Proteína 11 Semelhante a Bcl-2/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Dicroísmo Circular , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Humanos , Microscopia Eletrônica , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Proteínas Mitocondriais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Homologia de Sequência de Aminoácidos
2.
Men Masc ; 23(1): 104-126, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32742162

RESUMO

Gender-transformative interventions have been found to help ameliorate gender-inequitable norms and improve health outcomes for women and men. While narrative-based strategies are increasingly being used in public health programs, no evaluation publications exist to date for gender-transformative programming that employs men's public narrative-sharing as a central means for promoting healthy masculinities. The Men's Story Project (MSP) creates live productions in which diverse men publicly perform personal narratives that challenge hegemonic masculinity, promote gender equality, and highlight intersections of masculinity with other social identities. This study draws upon six focus groups with thirty-one audience members (AMs), two weeks after an MSP production at a US public university. The MSP led AMs to reevaluate key pillars of hegemonic masculinity, including a singular conception of masculinity, essentialist notions of gender, restricted emotional expression, and use of violence; AMs also gained an expanded understanding of intersectionality. Directions for future research are discussed.

3.
Glob Soc Welf ; 6(4): 245-257, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31929962

RESUMO

The Men's Story Project (MSP) is a scalable social and behavior change communication initiative that fosters critical reflection and dialogue about masculinities by creating public forums where men share non-fiction, personal narratives that challenge male norms and model healthy, gender-equitable masculinities. Via focus groups and in-depth interviews, this qualitative evaluation study examined impacts of the MSP for twenty MSP presenters and thirty-one college audience members who attended an MSP production at a public university in California in the Spring 2009 semester. Key thematic findings for MSP presenters included value placed on the men's group experience; having their stereotypes and prejudices challenged; empowerment and healing; reinforced commitment to cease/prevent men's violence; and expanded gender justice engagement. For audience members, key thematic findings included gaining an expanded conceptualization of masculinity; learning about intersectionality; having their stereotypes and prejudices challenged; and finding significant overall educational and social value in the MSP. The MSP's effects on audience members were facilitated by experiences of emotion, empathy, parafriendship and role modeling elicited by the first-person narratives, and the social learning environment fostered by the collective, public experience. Directions for further international research and practice are discussed.

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