The Mpv17l protein has two isoforms, M-LPL and M-LPS, which both regulate the production of reactive oxygen species (ROS) and protect against mitochondrial oxidative stress and apoptosis. M-LPL is ubiquitously expressed, while M-LPS is expressed mostly in the kidney of aged animals. We identified a variety of transcripts of the Mpv17l gene that could encode novel isoforms by mapping expressed sequence tags on the mouse M-LP genomic locus. We analysed the expression and evolutionary conservation of a novel Mpv17l transcript (mpv17l-002) that is predicted to encode a new protein, termed M-LP2. The isoform M-LP2 has the full length of M-LPS plus six amino acids at the end of its amino terminus, which could be encoded by an alternative 5'-flanking sequence. We show that the mRNA of M-LP2 has a different pattern of expression than the mRNA of M-LPS, and sequences of both transcripts are conserved in the rodent genome; however, neither of these isoforms is detected in the human genome. These observations suggest that the functions of certain M-LP isoforms are tissue- and species-specific, implying that their potential involvement in ROS metabolism may be redundant or may be complemented by other members of the Mpv17 family.
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http://dx.doi.org/10.1139/g09-061 | DOI Listing |
Acta Pharmacol Sin
January 2025
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, 221004, China.
Patients suffering epilepsy caused by the gain-of-function mutants of the hKCNT1 potassium channels are drug refractory. In this study, we cloned a novel human KCNT1B channel isoform using the brain cDNA library and conducted patch-clamp and molecular docking analyses to characterize the pharmacological properties of the hKCNT1B channel using thirteen drugs. Among cinchona alkaloids, we found that hydroquinine exerted the strongest blocking effect on the hKCNT1B channel, especially the F313L mutant.
View Article and Find Full Text PDFSci Rep
January 2025
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #04-06 Immunos, Singapore, 138648, Singapore.
The tumor suppressor LKB1/STK11 plays important roles in regulating cellular metabolism and stress responses and its mutations are associated with various cancers. We recently identified a novel exon 1b within intron 1 of human LKB1/STK11, which generates an alternatively spliced, mitochondria-targeting LKB1 isoform important for regulating mitochondrial oxidative stress. Here we examined the formation of this novel exon 1b and uncovered its relatively late emergence during evolution.
View Article and Find Full Text PDFThe Ca 3.2 isoform of T-type voltage-gated calcium channels plays a crucial role in regulating the excitability of nociceptive neurons; the endogenous molecules that modulate its activity, however, remain poorly understood. Here, we used serum proteomics and patch-clamp physiology to discover a novel peptide albumin (1-26) that facilitates channel gating by chelating trace metals that tonically inhibit Ca 3.
View Article and Find Full Text PDFUnlabelled: As the principal lipid transporter in the human brain, apolipoprotein E (ApoE) is tasked with the transport and protection of highly vulnerable lipids required to support and remodel neuronal membranes, in a process that is dependent on ApoE receptors. Human allele variants that encode proteins differing only in the number of cysteine (Cys)-to-arginine (Arg) exchanges (ApoE2 [2 Cys], ApoE3 [1 Cys], ApoE4 [0 Cys]) comprise the strongest genetic risk factor for sporadic Alzheimer's disease (AD); however, the molecular feature(s) and resultant mechanisms that underlie these isoform-dependent effects are unknown. One signature feature of Cys is the capacity to form disulfide (Cys-Cys) bridges, which are required to form disulfide bridge-linked dimers and multimers.
View Article and Find Full Text PDFComp Biochem Physiol C Toxicol Pharmacol
January 2025
Department of Zoology, University of Kerala, Kariavattom, Thiruvananthapuram 695581, Kerala, India; Inter-University Centre for Evolutionary and Integrative Biology-iCEIB, School of Life Sciences, University of Kerala, Kariavattom, Thiruvananthapuram 695 581, Kerala, India; Sastrajeevan Integrative Project, Centre for Integrative Stress and Ease-cRISE, Gregorian College of Advanced Studies, Sreekariyam, Thiruvananthapuram 695017, Kerala, India. Electronic address:
The cardiac actin cytoskeleton has a dynamic pattern of polymerisation. It is uncertain how far actin destabilisation impacts mitochondrial energetics and biogenesis, cell signal status, and structural entities in cardiomyocytes, particularly in hypoxic conditions. We thus tested the in vitro action of cytochalasin D (Cyt D), an inhibitor of actin polymerisation, in hypoxic ventricular explants to elucidate the role of the actin in mitochondrial energetics and biogenesis, cell signals and actin/tubulin/hsps/MMPs dynamics in hypoxic air-breathing fish hearts.
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