Bryostatin and its synthetic analog, picolog rescue dermal fibroblasts from prolonged stress and contribute to survival and rejuvenation of human skin equivalents

Abstract

Skin health is associated with the day-to-day activity of fibroblasts. The primary function of fibroblasts is to synthesize structural proteins, such as collagen, extracellular matrix proteins, and other proteins that support the structural integrity of the skin and are associated with younger, firmer, and more elastic skin that is better able to resist and recover from injury. At sub-nanomolar concentrations (0.03-0.3 nM), bryostatin-1 and its synthetic analog, picolog (0.1-10 nM) sustained the survival and activation of human dermal fibroblasts cultured under the stressful condition of prolonged serum deprivation. Bryostatin-1 treatment stabilized human skin equivalents (HSEs), a bioengineered combination of primary human skin cells (keratinocytes and dermal fibroblasts) on an extracellular matrix composed of mainly collagen. Fibroblasts activated by bryostatin-1 protected the structural integrity of HSEs. Bryostatin-1 and picolog prolonged activation of Erk in fibroblasts to promote cell survival. Chronic stress promotes the progression of apoptosis. Dermal fibroblasts constitutively express all components of Fas associated apoptosis, including caspase-8, an initiator enzyme of apoptosis. Prolong bryostatin-1 treatment reduced apoptosis by decreasing caspase-8 and protected dermal fibroblasts. Our data suggest that bryostatin-1 and picolog could be useful in anti-aging skincare, and could have applications in tissue engineering and regenerative medicine.

Unlocking the Drug Potential of the Bryostatin Family: Recent Advances in Product Synthesis and Biomedical Applications

“…Bryo 1 facilitated the activation and survival of human dermal fibroblasts under stressful conditions and promoted rejuvenationo fh ealthy skin. [42] The mechanisms of bryo 1 in human skin repair/protection processes are considered through activation of the expression of extracellular signal-regulated kinase (ERK) in fibroblasts to promote cell survival, reduction of apoptosis by decreasing the levels of the initiating enzyme (caspase-8),a nd protection of the structurali ntegrity of primary human skin cells( keratinocytes and dermal fibroblasts). Proteasomes can regulate protein homeostasisb yd egrading and eliminating unwanted/ damaged proteins.…”

“…In 2016 the group of Wender reported that the bryolog 73, termedp icolog, had similara ctivity to bryo 1 (mentionedi n section 2.5) in promoting the survival of dermal fibroblasts and improving skin health. [42] Figure 4. Bryostatin analogues synthesized in the period from 1998 to 2014.…”

“…Fibroblasts are responsible for the synthesis of structural proteins (e.g., collagen) that support the structural integrity of the skin and promote wound healing. Bryo 1 facilitated the activation and survival of human dermal fibroblasts under stressful conditions and promoted rejuvenation of healthy skin . The mechanisms of bryo 1 in human skin repair/protection processes are considered through activation of the expression of extracellular signal‐regulated kinase (ERK) in fibroblasts to promote cell survival, reduction of apoptosis by decreasing the levels of the initiating enzyme (caspase‐8), and protection of the structural integrity of primary human skin cells (keratinocytes and dermal fibroblasts).…”

Protein kinase C activator bryostatin‐1 modulates proteasome function

“…In a recent study we found that at subnanomolar concentrations (0.03-0.3 nM), bryostatin-1 and its synthetic analog, picolog (0.1-10 nM) sustained the survival and activation of human dermal fibroblasts cultured under the stressful condition of prolonged serum deprivation. 29 In the same study, we also reported that bryostatin-1 treatment stabilized human skin equivalents (HSEs), a bioengineered combination of primary human skin cells (keratinocytes and dermal fibroblasts) on an extracellular matrix composed of mainly collagen by inducing prolonged activation of Erk in fibroblasts, which promotes cell survival. Moreover, prolonged bryostatin-1 treatment reduces apoptosis by decreasing caspase-8 and protects dermal fibroblasts.…”

Przegląd Technik Diagnostyki Skóry W Oparciu O Modele Wielowarstwowe Skóry I Spektrofotometrię

“…Human skin is mainly made of these elements, so it is worth paying attention to the shapes of their absorption spectrum. It is on the basis of spectre and developed models that diagnostic decisions are made [15,17]. To receive a full diagnosis, it is necessary to know the anatomical structure of human skin, the processes of the influence of ultraviolet radiation, visible light and near infrared in each layer of the skin.…”