RESUMO
A sharp drop in lenticular glutathione (GSH) plays a pivotal role in age-related cataract (ARC) formation. Despite recognizing GSH's importance in lens defense for decades, its decline with age remains puzzling. Our recent study revealed an age-related truncation affecting the essential GSH biosynthesis enzyme, the γ-glutamylcysteine ligase catalytic subunit (GCLC), at aspartate residue 499. Intriguingly, these truncated GCLC fragments compete with full-length GCLC in forming a heterocomplex with the modifier subunit (GCLM) but exhibit markedly reduced enzymatic activity. Crucially, using an aspartate-to-glutamate mutation knock-in (D499E-KI) mouse model that blocks GCLC truncation, we observed a notable delay in ARC formation compared to WT mice: Nearly 50% of D499E-KI mice remained cataract-free versus ~20% of the WT mice at their age of 20 months. Our findings concerning age-related GCLC truncation might be the key to understanding the profound reduction in lens GSH with age. By halting GCLC truncation, we can rejuvenate lens GSH levels and considerably postpone cataract onset.
Assuntos
Envelhecimento , Domínio Catalítico , Catarata , Glutamato-Cisteína Ligase , Glutationa , Cristalino , Catarata/patologia , Catarata/genética , Catarata/metabolismo , Animais , Glutamato-Cisteína Ligase/metabolismo , Glutamato-Cisteína Ligase/genética , Camundongos , Glutationa/metabolismo , Cristalino/metabolismo , Cristalino/patologia , Envelhecimento/metabolismo , Humanos , Modelos Animais de Doenças , Mutação , Técnicas de Introdução de GenesRESUMO
CatSper1 and TNP2 genes are known to affect semen quality and fertility parameters, including sperm motility and maturation. However, studies are yet to examine the genes in indigenous and crossbred cattle in Bangladesh. Therefore, this study was conducted to determine the genetic variants of CatSper1 and TNP2 in indigenous and crossbred cattle in Bangladesh. Blood samples were collected from 130 indigenous and 70 crossbred (Holstein Friesian × indigenous) cattle. Nucleotide variation was evaluated by PCR-RFLP and sequencing. The results of the study showed that the indigenous cattle possessed only TT genotype (1.0), whereas the crossbreds possessed both TT (0.91) and CT (0.09) genotypes, which was validated by gene sequencing. Additionally, the CatSper1 was conserved in both the indigenous and crossbred cattle, suggesting good semen quality and fertility. However, the TNP2 was conserved in the indigenous breeds and mostly conserved in the crossbreds. The findings of this study reveal the diversity of CatSper1 and TNP2 genes in indigenous and crossbred cattle.
