Overexpression of CBS and CSE genes affects lifespan, stress resistance and locomotor activity in Drosophila melanogaster

Abstract

Recent experimental studies highlighted the role of hydrogen sulfide (H₂S) in aging and longevity. The cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE) are the key enzymes responsible for H₂S production. Here we investigated the geroprotective effects of CSE and CBS overexpression in Drosophila. Overexpression of CSE did not affect a lifespan and decrease (mitochondrial form of CSE) or increase (cytoplasmic form of CSE) age dynamics of locomotor activity, while overexpression of CBS increase median (by 12.5%) and maximum (by 6.9%) lifespan and locomotor activity. Increasing of both CSE and CBS expression levels resulted in thermotolerance, but the resistance to combination of arid and food-free conditions decreased. The resistance to oxidative stress (paraquat) was not affected in flies with overexpression of CBS and cytoplasmic CSE, but decreased in flies overexpressing mitochondrial form of CSE. Thus, transgene overexpression of the CSE and CBS in Drosophila induce similar effects on stress-resistance and locomotor activity, however lifespan extending effect was revealed for CBS overexpression only.

Keywords: Drosophila; desiccation; hydrogen sulfide; hyperthermia; lifespan; locomotor activity; paraquat; starvation.

Figure 1

The effects of constitutive ubiquitous overexpression of CSE[LD22661] (A), CSE[LD22255] (B), CBS[LD21426] (C) on lifespan. *p<0.05, **p<0.01, ***p<0.001, da-GAL4>UAS vs da-GAL4; ^#p<0.05, ^##p<0.01, ^###p<0.001, da-GAL4>UAS vs UAS, Kolmogorov-Smirnov test.

Figure 2

The effects of constitutive ubiquitous overexpression of CSE and CBS genes on resistance to stress factors (paraquat (A-C), hyperthermia (D-F) and combination of arid and food-free conditions (G-I)). *p<0.05, **p<0.01, ***p<0.001, Fisher's exact test (da-GAL4>UAS vs da-GAL4); #p<0.05, ##p<0.01, ###p<0.001, Fisher's exact test (da-GAL4>UAS vs UAS).

Figure 3

The effects of constitutive ubiquitous overexpression of CSE[LD22661] (A), CSE[LD22255] (B), CBS[LD21426] (C) on age-dependent changes in spontaneous locomotor activity. Locomotor activity was defined as averaged number of sensor crosses during 3 min by 30 flies. *р<0.05, **р<0.01, ***р<0.001, χ².

Figure 4

The possible mechanisms of CBS and CSE overexpression on lifespan, stress resistance and locomotor activity. ROS – reactive oxygen species. Please note that this scheme serve as generalized illustration and the mechanisms are dependent on the experimental system and model organism used. For detailed description of these mechanisms see [–10].