Cardiomyocyte-specific deletion of GCN5L1 reduces lysine acetylation and attenuates diastolic dysfunction in aged mice by improving cardiac fatty acid oxidation
Biochem J. 2024 Feb 23:BCJ20230421. doi: 10.1042/BCJ20230421. Online ahead of print.ABSTRACTCardiac mitochondrial dysfunction is a critical contributor to the pathogenesis of aging and many age-related conditions. As such, complete control of mitochondrial function is critical to maintain cardiac efficiency in the aged heart. Lysine acetylation is a reversible post-translational modification shown to regulate several mitochondrial metabolic and biochemical processes. In the present study, we investigated how mitochondrial lysine acetylation regulates fatty acid oxidation and cardiac function in the aged heart. We found a s...
Source: The Biochemical Journal - February 23, 2024 Category: Biochemistry Authors: Jackson E Stewart Jenna M Crawford William E Mullen Angelica Jacques Michael W Stoner Iain Scott Dharendra Thapa Source Type: research
Cardiomyocyte-specific deletion of GCN5L1 reduces lysine acetylation and attenuates diastolic dysfunction in aged mice by improving cardiac fatty acid oxidation
Biochem J. 2024 Feb 23:BCJ20230421. doi: 10.1042/BCJ20230421. Online ahead of print.ABSTRACTCardiac mitochondrial dysfunction is a critical contributor to the pathogenesis of aging and many age-related conditions. As such, complete control of mitochondrial function is critical to maintain cardiac efficiency in the aged heart. Lysine acetylation is a reversible post-translational modification shown to regulate several mitochondrial metabolic and biochemical processes. In the present study, we investigated how mitochondrial lysine acetylation regulates fatty acid oxidation and cardiac function in the aged heart. We found a s...
Source: The Biochemical Journal - February 23, 2024 Category: Biochemistry Authors: Jackson E Stewart Jenna M Crawford William E Mullen Angelica Jacques Michael W Stoner Iain Scott Dharendra Thapa Source Type: research
Reporter cell lines to screen for inhibitors or regulators of the KRAS-RAF-MEK1/2-ERK1/2 pathway
Biochem J. 2024 Feb 21:BCJ20240015. doi: 10.1042/BCJ20240015. Online ahead of print.ABSTRACTThe RAS-regulated RAF-MEK1/2-ERK1/2 signalling pathway is activated in cancer due to mutations in RAS proteins (especially KRAS), BRAF, CRAF, MEK1 and MEK2. Whilst inhibitors of KRASG12C (lung adenocarcinoma) and BRAF and MEK1/2 (melanoma and colorectal cancer) are clinically approved, acquired resistance remains a problem. Consequently, the search for new inhibitors (especially of RAS proteins), new inhibitor modalities and regulators of this pathway, which may be new drug targets, continues and increasingly involves cell-based scr...
Source: The Biochemical Journal - February 21, 2024 Category: Biochemistry Authors: Laura Weatherdon Kate Stuart Megan A Cassidy Alberto Moreno de la G ándara Hanneke Okkenhaug Markus Muellener Grahame Mckenzie Simon J Cook Rebecca Gilley Source Type: research
Reporter cell lines to screen for inhibitors or regulators of the KRAS-RAF-MEK1/2-ERK1/2 pathway
Biochem J. 2024 Feb 21:BCJ20240015. doi: 10.1042/BCJ20240015. Online ahead of print.ABSTRACTThe RAS-regulated RAF-MEK1/2-ERK1/2 signalling pathway is activated in cancer due to mutations in RAS proteins (especially KRAS), BRAF, CRAF, MEK1 and MEK2. Whilst inhibitors of KRASG12C (lung adenocarcinoma) and BRAF and MEK1/2 (melanoma and colorectal cancer) are clinically approved, acquired resistance remains a problem. Consequently, the search for new inhibitors (especially of RAS proteins), new inhibitor modalities and regulators of this pathway, which may be new drug targets, continues and increasingly involves cell-based scr...
Source: The Biochemical Journal - February 21, 2024 Category: Biochemistry Authors: Laura Weatherdon Kate Stuart Megan A Cassidy Alberto Moreno de la G ándara Hanneke Okkenhaug Markus Muellener Grahame Mckenzie Simon J Cook Rebecca Gilley Source Type: research
Reporter cell lines to screen for inhibitors or regulators of the KRAS-RAF-MEK1/2-ERK1/2 pathway
Biochem J. 2024 Feb 21:BCJ20240015. doi: 10.1042/BCJ20240015. Online ahead of print.ABSTRACTThe RAS-regulated RAF-MEK1/2-ERK1/2 signalling pathway is activated in cancer due to mutations in RAS proteins (especially KRAS), BRAF, CRAF, MEK1 and MEK2. Whilst inhibitors of KRASG12C (lung adenocarcinoma) and BRAF and MEK1/2 (melanoma and colorectal cancer) are clinically approved, acquired resistance remains a problem. Consequently, the search for new inhibitors (especially of RAS proteins), new inhibitor modalities and regulators of this pathway, which may be new drug targets, continues and increasingly involves cell-based scr...
Source: The Biochemical Journal - February 21, 2024 Category: Biochemistry Authors: Laura Weatherdon Kate Stuart Megan A Cassidy Alberto Moreno de la G ándara Hanneke Okkenhaug Markus Muellener Grahame Mckenzie Simon J Cook Rebecca Gilley Source Type: research
Novel modifications of PARP inhibitor veliparib increase PARP1 binding to DNA breaks
Biochem J. 2024 Feb 19:BCJ20230406. doi: 10.1042/BCJ20230406. Online ahead of print.ABSTRACTCatalytic poly(ADP-ribose) production by PARP1 is allosterically activated through interaction with DNA breaks, and PARP inhibitor compounds have the potential to influence PARP1 allostery in addition to preventing catalytic activity. Using the benzimidazole-4-carboxamide pharmacophore present in the first generation PARP1 inhibitor veliparib, a series of eleven derivatives was designed, synthesized, and evaluated as allosteric PARP1 inhibitors, with the premise that bulky substituents would engage the HD regulatory domain and there...
Source: The Biochemical Journal - February 19, 2024 Category: Biochemistry Authors: Uday Kiran Velagapudi Élise Rouleau-Turcotte Ramya Billur Xuwei Shao Manisha Patil Ben E Black John Pascal Tanaji T Talele Source Type: research
Colonic ketogenesis, a microbiota-regulated process, contributes to blood ketones and protects against colitis in mice
Biochem J. 2024 Feb 21;481(4):295-312. doi: 10.1042/BCJ20230403.ABSTRACTKetogenesis is considered to occur primarily in liver to generate ketones as an alternative energy source for non-hepatic tissues when glucose availability/utilization is impaired. 3-Hydroxy-3-methylglutaryl-CoA synthase-2 (HMGCS2) mediates the rate-limiting step in this mitochondrial pathway. Publicly available databases show marked down-regulation of HMGCS2 in colonic tissues in Crohn's disease and ulcerative colitis. This led us to investigate the expression and function of this pathway in colon and its relevance to colonic inflammation in mice. Hmg...
Source: The Biochemical Journal - February 19, 2024 Category: Biochemistry Authors: Kevin Bass Sathish Sivaprakasam Gunadharini Dharmalingam-Nandagopal Muthusamy Thangaraju Vadivel Ganapathy Source Type: research
Mesenteric artery smooth muscle cells from hypertensive rats have increased microtubule acetylation
Conclusions:</p> Acetylation of tubulin at Lys40 is elevated in mesenteric arteries from the SHR. Furthermore, this study shows that tubacin has an endothelial-dependent bimodal effect on isoprenaline-mediated vasorelaxation.PMID:38373073 | DOI:10.1042/BCJ20230420 (Source: The Biochemical Journal)
Source: The Biochemical Journal - February 19, 2024 Category: Biochemistry Authors: Anthony M Mozzicato Joakim A Bastrup Jose L Sanchez Alonso Jennifer van der Horst Julia Gorelik Per M årten Hägglund Thomas Jepps Source Type: research
Novel modifications of PARP inhibitor veliparib increase PARP1 binding to DNA breaks
Biochem J. 2024 Feb 19:BCJ20230406. doi: 10.1042/BCJ20230406. Online ahead of print.ABSTRACTCatalytic poly(ADP-ribose) production by PARP1 is allosterically activated through interaction with DNA breaks, and PARP inhibitor compounds have the potential to influence PARP1 allostery in addition to preventing catalytic activity. Using the benzimidazole-4-carboxamide pharmacophore present in the first generation PARP1 inhibitor veliparib, a series of eleven derivatives was designed, synthesized, and evaluated as allosteric PARP1 inhibitors, with the premise that bulky substituents would engage the HD regulatory domain and there...
Source: The Biochemical Journal - February 19, 2024 Category: Biochemistry Authors: Uday Kiran Velagapudi Élise Rouleau-Turcotte Ramya Billur Xuwei Shao Manisha Patil Ben E Black John Pascal Tanaji T Talele Source Type: research
Colonic ketogenesis, a microbiota-regulated process, contributes to blood ketones and protects against colitis in mice
Biochem J. 2024 Feb 21;481(4):295-312. doi: 10.1042/BCJ20230403.ABSTRACTKetogenesis is considered to occur primarily in liver to generate ketones as an alternative energy source for non-hepatic tissues when glucose availability/utilization is impaired. 3-Hydroxy-3-methylglutaryl-CoA synthase-2 (HMGCS2) mediates the rate-limiting step in this mitochondrial pathway. Publicly available databases show marked down-regulation of HMGCS2 in colonic tissues in Crohn's disease and ulcerative colitis. This led us to investigate the expression and function of this pathway in colon and its relevance to colonic inflammation in mice. Hmg...
Source: The Biochemical Journal - February 19, 2024 Category: Biochemistry Authors: Kevin Bass Sathish Sivaprakasam Gunadharini Dharmalingam-Nandagopal Muthusamy Thangaraju Vadivel Ganapathy Source Type: research
Mesenteric artery smooth muscle cells from hypertensive rats have increased microtubule acetylation
Conclusions:</p> Acetylation of tubulin at Lys40 is elevated in mesenteric arteries from the SHR. Furthermore, this study shows that tubacin has an endothelial-dependent bimodal effect on isoprenaline-mediated vasorelaxation.PMID:38373073 | DOI:10.1042/BCJ20230420 (Source: The Biochemical Journal)
Source: The Biochemical Journal - February 19, 2024 Category: Biochemistry Authors: Anthony M Mozzicato Joakim A Bastrup Jose L Sanchez Alonso Jennifer van der Horst Julia Gorelik Per M årten Hägglund Thomas Jepps Source Type: research
The role of filamentous matrix molecules in shaping the architecture and emergent properties of bacterial biofilms
Biochem J. 2024 Feb 21;481(4):245-263. doi: 10.1042/BCJ20210301.ABSTRACTNumerous bacteria naturally occur within spatially organised, multicellular communities called biofilms. Moreover, most bacterial infections proceed with biofilm formation, posing major challenges to human health. Within biofilms, bacterial cells are embedded in a primarily self-produced extracellular matrix, which is a defining feature of all biofilms. The biofilm matrix is a complex, viscous mixture primarily composed of polymeric substances such as polysaccharides, filamentous protein fibres, and extracellular DNA. The structured arrangement of the ...
Source: The Biochemical Journal - February 15, 2024 Category: Biochemistry Authors: Jan B öhning Abul K Tarafder Tanmay A M Bharat Source Type: research
The role of filamentous matrix molecules in shaping the architecture and emergent properties of bacterial biofilms
Biochem J. 2024 Feb 21;481(4):245-263. doi: 10.1042/BCJ20210301.ABSTRACTNumerous bacteria naturally occur within spatially organised, multicellular communities called biofilms. Moreover, most bacterial infections proceed with biofilm formation, posing major challenges to human health. Within biofilms, bacterial cells are embedded in a primarily self-produced extracellular matrix, which is a defining feature of all biofilms. The biofilm matrix is a complex, viscous mixture primarily composed of polymeric substances such as polysaccharides, filamentous protein fibres, and extracellular DNA. The structured arrangement of the ...
Source: The Biochemical Journal - February 15, 2024 Category: Biochemistry Authors: Jan B öhning Abul K Tarafder Tanmay A M Bharat Source Type: research
The role of filamentous matrix molecules in shaping the architecture and emergent properties of bacterial biofilms
Biochem J. 2024 Feb 21;481(4):245-263. doi: 10.1042/BCJ20210301.ABSTRACTNumerous bacteria naturally occur within spatially organised, multicellular communities called biofilms. Moreover, most bacterial infections proceed with biofilm formation, posing major challenges to human health. Within biofilms, bacterial cells are embedded in a primarily self-produced extracellular matrix, which is a defining feature of all biofilms. The biofilm matrix is a complex, viscous mixture primarily composed of polymeric substances such as polysaccharides, filamentous protein fibres, and extracellular DNA. The structured arrangement of the ...
Source: The Biochemical Journal - February 15, 2024 Category: Biochemistry Authors: Jan B öhning Abul K Tarafder Tanmay A M Bharat Source Type: research
Beyond the tail: the consequence of context in histone post-translational modification and chromatin research
Biochem J. 2024 Feb 21;481(4):219-244. doi: 10.1042/BCJ20230342.ABSTRACTThe role of histone post-translational modifications (PTMs) in chromatin structure and genome function has been the subject of intense debate for more than 60 years. Though complex, the discourse can be summarized in two distinct - and deceptively simple - questions: What is the function of histone PTMs? And how should they be studied? Decades of research show these queries are intricately linked and far from straightforward. Here we provide a historical perspective, highlighting how the arrival of new technologies shaped discovery and insight. Despite...
Source: The Biochemical Journal - February 14, 2024 Category: Biochemistry Authors: Ellen N Weinzapfel Karlie N Fedder-Semmes Zu-Wen Sun Michael-Christopher Keogh Source Type: research
