ROS-dependent Bax/Bcl2 and caspase 3 pathway-mediated apoptosis induced by zineb in human keratinocyte cells

Abstract

There are a large number of agricultural workers who are exposed to pesticides through skin and inhalation. The best approach to identify altered molecular pathways during dermal exposure to pesticides is relevant to risk-associated concern about skin safety. In this study, we investigated the cytotoxic effect of zineb, a fungicide, in human keratinocyte (HaCaT) cells. HaCaT cells were treated with zineb (1–40 µg/mL) for 24 hours. Cellular and molecular mechanisms of cell toxicity were investigated through MTT and neutral red-uptake assays. Zineb reduced viability of HaCaT cells and induced apoptosis in a concentration-dependent manner. Zineb increased levels of Bax and caspase 3 and inhibited the level of Bcl2, which subsequently induced apoptosis via the Bax/Bcl2 and caspase pathway. Therefore, zineb could have induced apoptosis through the mitochondrial pathway in HaCaT cells. Our study suggests that zineb is cytotoxic to HaCaT cells via the induction of apoptosis and oxidative stress in vitro.

Field rates of Sivanto™ (flupyradifurone) and Transform® (sulfoxaflor) increase oxidative stress and induce apoptosis in honey bees (Apis mellifera L.)

“…Increased systemic oxidative stress, generated by higher levels of ROS/RNS, can play an important role in pesticide toxicity [28][29][30]. High ROS/RNS levels are also indicative of an onset of apoptosis [30][31][32]. Apoptosis is a form of programmed cell death [33].…”

Insight into the mechanism of aspartame‐induced toxicity in male reproductive system following long‐term consumption in mice model

“…Indeed, apoptosis, albeit at the physiologic level (20%), eventually conserves the spermatogenesis through several families of genes and proteins, in which the Bcl‐2 controlled pathway is the key mechanism to execute the physiologically impaired cells 18 . In line, different intracellular stresses, cytokines deprivation, inflammation, radiation and growth factor withdrawal are known to evoke the Bcl‐2‐controlled apoptosis 18,19 . Bcl‐2, an antiapoptotic protein, by preventing the Bax (proapoptotic protein) oligomerization and/or binding to Bax (making Bcl‐2/Bax complex) inactivates the Bax and consequently prevents the cytochrome c release from mitochondrion into the cytoplasm.…”

“…18 In line, different intracellular stresses, cytokines deprivation, inflammation, radiation and growth factor withdrawal are known to evoke the Bcl-2-controlled apoptosis. 18,19 Bcl-2, an antiapoptotic protein, by preventing the Bax (proapoptotic protein) oligomerization and/or binding to Bax (making Bcl-2/Bax complex) inactivates the Bax and consequently prevents the cytochrome c release from mitochondrion into the cytoplasm.…”

Ginkgo biloba delays light‑induced photoreceptor degeneration through antioxidant and antiapoptotic properties

“…The cell death mechanism is initiated by the translocation of Bax and Bak to the mitochondrial membrane, and Cyc release into the cytosol (50,51). This initiates the activation of cleaved caspase-3, suppressing Bcl2, and induces morphological and biochemical changes in the retina (25,26). The results of the present study indicated that exposure to light upregulated the levels of Cyc, Bak-1, Bax and cleaved caspase-3 in the retina, while this process was inhibited following pretreatment of the mice with EGb 761.…”

“…Apoptosis occurs via the activation of the Bax-dependent mitochondrial cascade, which releases cytochrome c (Cyc) into the cytoplasm and consequently initiates the activation of cleaved caspase-3 (15,24,25). This suppresses Bcl2, induces apoptosis via the Bax/Bcl2 and caspase-mediated signaling pathways, and leads to retinal degeneration (25,26). As discussed in previous studies, pretreatment with EGb-761 decreases cell death via the Bax/Bcl2 signaling pathway and exerts a protective effect against apoptosis that delays photoreceptor degeneration (27,28).…”